Method and system for nerve stimulation and cardiac sensing prior to and during a medical procedure

ABSTRACT

A method of performing a medical procedure, such as surgery, is provided. A nerve is stimulated in order to adjust the beating of the heart to a first condition, such as a stopped or slowed condition. The medical procedure is performed on the heart or another organ. The stimulation of the nerve is stopped in order to adjust the beating of the heart to a second condition, such as a beating condition. The heart itself may also be stimulated to a beating condition, such as by pacing. The stimulation of the nerve may be continued in order to allow the medical procedure to be continued. A sensor to sense a characteristic of a fluid or tissue, such as an impending contraction, may be also used during the medical procedure. Systems and devices for performing the medical procedure are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. Ser. No.10/207,725 filed Jul. 29, 2002, which is a continuation-in-part of U.S.Ser. No. 09/670,441 filed Sep. 26, 2000, now U.S. Pat. No. 6,449,507which is a continuation-in-part of U.S. Ser. No. 09/433,323 filed Nov.13, 1999, now U.S. Pat. No. 6,266,564, which is a continuation of U.S.Ser. No. 09/070,506 filed Apr. 30, 1998, now U.S. Pat. No. 6,006,134which is a continuation-in-part of U.S. Ser. No. 08/640,013 filed Apr.30, 1996, now abandoned, and is also a continuation-in-part of U.S. Ser.No. ______, filed Jul. 29, 2003 which is a divisional of U.S. Ser. No.09/669,355, filed Sep. 26, 2000, now U.S. Pat. No. 6,628,987, and isalso a continuation-in-part of U.S. Ser. No. 10/421,459, filed Apr. 23,2003 which is a continuation of U.S. Ser. No. 09/669,961 filed Sep. 26,2000 and is also a continuation-in-part of U.S. Ser. No. ______, filedSep. 8, 2003, which is a continuation of U.S. Ser. No. 10/408,647, filedApr. 7, 2003 which is a continuation of U.S. Ser. No. 09/670,440, filedSep. 26, 2000, now abandoned.

FIELD OF THE INVENTION

[0002] This invention relates to methods and systems for performing amedical procedure, especially a procedure during which it is necessaryto adjust the beating of the heart in order to allow the medicalprocedure to be performed on the heart or another organ. Moreparticularly, this invention relates to methods and systems ofstimulating a nerve in order to modify the beating of a heart to allow amedical procedure to be performed or for blood flow to be controlled.This invention also relates to methods and systems for sensing imminentcardiac contractions during such a procedure. In addition, thisinvention relates to methods and systems for monitoring and controllingone or more physiological and/or chemical parameters of a fluid such asblood or oxygen in the systemic and/or pulmonary circulatory systemsduring a medical procedure.

BACKGROUND OF THE INVENTION

[0003] The current leading cause of death in the United States iscoronary artery disease in which the coronary arteries are blocked byatherosclerotic plaques or deposits of fat. The typical treatment torelieve a partially or fully blocked coronary artery is coronary arterybypass graph (CABG) surgery.

[0004] CABG surgery, also known as “heart bypass” surgery, generallyentails using a graph to bypass the coronary obstruction. The procedureis generally lengthy, traumatic and subject to patient risks. Among therisk factors involved is the use of a cardiopulmonary bypass (CPB)circuit, also known as a “heart-lung machine,” to pump blood andoxygenate the blood so that the patient's heart may be stopped duringthe surgery.

[0005] Conventional CABG procedures are typically conducted on a stoppedheart while the patient is on a (CPB) circuit. A stopped heart and a CPBcircuit enables a surgeon to work in a bloodless, still operative field.However, there are a number of problems associated with CABG proceduresperformed while on CPB including the initiation of a systemicinflammatory response due to interactions of blood elements with theartificial material surfaces of the CPB circuit and global myocardialischemia due to cardioplegic cardiac arrest. For these reasons, avoidingthe use of CPB or cardioplegic cardiac arrest may help minimizepost-operative complications.

[0006] One method, as disclosed in U.S. Pat. No. 5,651,378 to inventorsMatheny and Taylor and in U.S. Pat. No. 5,913,876 to inventors Taylor etal., for facilitating coronary bypass surgery on a beating heart andthereby avoid the use of CPB and cardioplegic cardiac arrest includesstimulating the vagal nerve electrically in order to temporarily stop orsubstantially reduce the beating of the heart. This may be followed bypacing the heart to start its beating.

[0007] Another method, as disclosed in two published PCT applications,WO 99/09971 and WO 99/09973, both to inventor Puskas, involves stoppingthe beating of the heart during coronary bypass surgery using electricalstimulation of the vagal nerve in combination with administration ofdrugs. Another method, as disclosed in U.S. Pat. No. 6,060,454 toinventor Duhaylongsod, involves stopping the beating of the heart duringcoronary bypass surgery via the local delivery of drugs to the heart.

[0008] Although it is desirable to stop the heart for a period of timein order to allow the surgeon to accomplish a required task withoutinterference from heart movement, i.e. a motionless operative field, itis undesirable to have the heart stopped for too long a period of timesince the body needs, among other things, a constant supply of oxygen.In fact, it is particularly important to maintain sufficient blood flow,and therefore oxygen flow, to the brain. A system for sensing biologicalparameters, such as the amount of blood flow or oxygen flow to thebrain, could help determine whether these parameters are sufficientduring a medical procedure. Stopping the heart for prolonged periods oftime may cause damage to the patient.

[0009] Moreover, once stopped or still, the heart may still contractoccasionally. This is sometimes referred to as an “escape beat.” Such an“escape beat” may occur without any warning to the surgeon and themovement associated with the escape beat may interfere with the medicalprocedure being carried out.

[0010] In addition, the field in which the invention is to be performedmay be limited in size. For example, when surgery is performed on aparticular blood vessel, the vessel's size is usually quite small and agreat deal of precision is required to perform the surgery or even tolocate the vessel. Such precision requires more time during which theheart is stopped.

SUMMARY OF THE INVENTION

[0011] One aspect of the present invention provides a method ofperforming a medical procedure wherein the method includes stimulating anerve to adjust the beating of the heart to a first condition. A medicalprocedure is then performed on an organ. Stimulation of the nerve isthen reduced to adjust the beating of a heart to a second condition. Thenerve is then stimulated a subsequent time in order to re-adjust thebeating of the heart to the first condition and then the medicalprocedure is continued. Nerve stimulation may be stopped to achieve thesecond condition. The first condition may be a stopped or a slowedcondition. The second condition may be a beating condition. The heartmay also be stimulated to adjust the beating of the heart to the secondcondition. The heart may be stimulated by pacing.

[0012] Another aspect of the present invention provides a system forperforming a medical procedure wherein the system includes a nervestimulator to inhibit beating of the heart and a cardiac stimulator incommunication with the nerve stimulator to stimulate beating of theheart. The system may also include drug delivery means for delivering atleast one drug during the medical procedure.

[0013] Another aspect of the present invention provides a device forperforming a medical procedure wherein the device includes a processorconnected to a nerve stimulation electrode and a cardiac stimulationelectrode. The processor processes out put from the nerve stimulationelectrode and adjusts output from the cardiac stimulation electrodebased on output from the nerve stimulation electrode. Stimulation fromthe nerve stimulation electrode may occur in an inverse relationship tostimulation from the cardiac stimulation electrode.

[0014] Another aspect of the present invention provides a system forperforming a medical procedure wherein the system includes a sensor tosense a biological characteristic, a nerve stimulator to inhibit beatingof a heart when the sensor senses the biological characteristic at afirst value and a cardiac stimulator to stimulate beating of the heartwhen the sensor senses the biological characteristic at a second value.

[0015] The biological characteristic may be a chemical characteristic ofa tissue, a chemical characteristic of a fluid, a physicalcharacteristic of a tissue, a physical characteristic of a fluid, aphysiological characteristic of a tissue, and a physiologicalcharacteristic of a fluid. The biological characteristic may be acharacteristic of a body component such as the blood, cardiac tissue, ora nerve. The biological characteristic may be fluid flow, fluidpressure, mechanical pressure, temperature, electrical current,temperature, chemical concentration, presence of a peptide,concentration of a peptide, presence of a protein, concentration of aprotein, a metabolic process, presence of a gas, concentration of a gas,presence of oxygen, concentration of a oxygen, presence of carbondioxide, concentration of carbon dioxide.

[0016] The system may also include drug delivery means such as a spray,a cream, an ointment, a medicament, a pill, a patch, a catheter, acannula, a needle and syringe, a pump, and an iontophoretic drugdelivery device to deliver at least one drug during the procedure. Thedrug may be a beta-blocker, a cholinergic agent, a cholinesteraseinhibitor, a calcium channel blocker, a sodium channel blocker, apotassium channel agent, adenosine, an adenosine receptor agonist, anadenosine deaminase inhibitor, dipyridamole, a monoamine oxidaseinhibitor, digoxin, digitalis, lignocaine, a bradykinin agent, aserotoninergic agonist, an antiarrythmic agent, a cardiac glycoside, alocal anesthetic, atropine, a calcium solution, an agent that promotesheart rate, an agent that promotes heart contractions, dopamine, acatecholamine, an inotrope glucagon, a hormone, forskolin, epinephrine,norepinephrine, thyroid hormone, a phosphodiesterase inhibitor,prostacyclin, prostaglandin and a methylxanthine, may be deliveredduring the procedure. The drug may be naturally occurring or chemicallysynthesized.

[0017] The nerve stimulator may stimulate a nerve such as a vagal nerve,a carotid sinus nerve, a fat pad. The nerve stimulator may be stoppedautomatically when the sensor senses the biological characteristic atthe second value. Cardiac stimulation may begin automatically when thesensor senses the biological characteristic at the second value. Thenerve stimulator may be, for example, one or more electrodes such asnerve stimulation electrodes, endotracheal electrodes, endoesophagealelectrodes, intravascular electrodes, transcutaneous electrodes,intracutaneous electrodes, balloon-type electrodes, basket-typeelectrodes, umbrella-type electrodes, tape-type electrodes, suction-typeelectrodes, screw-type electrodes, barb-type electrodes, bipolarelectrodes, monopolar electrodes, metal electrodes, wire electrodes,patch electrodes, cuff electrodes, clip electrodes, needle electrodesand probe electrodes.

[0018] The sensor may be an imaging system, an electrical sensor; achemical sensor, an electromagnetic interference sensor, anelectrochemical sensor; a pressure sensor, a sound wave sensor; amagnetic sensor; an ultraviolet sensor; a visible light sensor; aninfrared sensor; a radiation sensor; a flow sensor; a temperaturesensor, a gas sensor, an optical sensor, a pH sensor, a potentiometricsensor, a fluorescence sensor and a biosensor.

[0019] The cardiac stimulator may be, for example, one or moreelectrodes such as cardiac stimulation electrodes, clip electrodes,needle electrodes, probe electrodes, pacing electrodes, epicardialelectrodes, patch electrodes, intravascular electrodes, balloon-typeelectrodes, basket-type electrodes, tape-type electrodes, umbrella-typeelectrodes, suction-type electrodes, endotracheal electrodes,endoesophageal electrodes, transcutaneous electrodes, intracutaneouselectrodes, screw-type electrodes, barb-type electrodes, bipolarelectrodes, monopolar electrodes, metal electrodes, wire electrodes andcuff electrodes.

[0020] The system may also include a breathing regulator, which maycontrol a respirator. The breathing regulator may stimulate a phrenicnerve. The breathing regulator may be, for example, one or moreelectrodes such as nerve stimulation electrodes, endotrachealelectrodes, endoesophageal electrodes, intravascular electrodes,transcutaneous electrodes, intracutaneous electrodes, balloon-typeelectrodes, basket-type electrodes, umbrella-type electrodes, tape-typeelectrodes, suction-type electrodes, screw-type electrodes, barb-typeelectrodes, bipolar electrodes, monopolar electrodes, metal electrodes,wire electrodes, patch electrodes, cuff electrodes, clip electrodes,needle electrodes and probe electrodes.

[0021] The medical procedure may be a surgical procedure, a non-surgicalprocedure, a fluoroscopic procedure, a cardiac procedure, a vascularprocedure a neurosurgical procedure, an electrophysiological procedure,a diagnostic procedure, a therapeutic procedure, an ablation procedure,an endovascular procedure, a liver procedure, a spleen procedure, apulmonary procedure, an aneurysm repair, an imaging procedure, a CATscan procedure, a MRI procedure, a pharmacological therapy, a drugdelivery procedure, biological delivery procedure, a genetic therapy, acellular therapy, a cancer therapy, a radiation therapy, atransplantation procedure, a coronary angioplasty procedure, a stentdelivery procedure, an atherectomy procedure, a procedure that requiresprecise control of cardiac motion, a procedure that requires precisecontrol of bleeding, a non-invasive procedure, a minimally invasiveprocedure, an invasive procedure, a port-access, an endoscopicprocedure, a sternotomy procedure, a thoracotomy procedure and a roboticprocedure.

[0022] Another aspect of the present invention provides a method forperforming a medical procedure wherein a biological characteristic issensed at a first value and a first signal related to the sensedbiological characteristic is sent. Beating of a heart is inhibited inresponse to the first signal. The medical procedure is then performed.The biological characteristic is then sensed at a second value and asecond signal related to the sensed biological characteristic at thesecond value is sent. Beating of the heart is stimulated in response tothe second signal.

[0023] Beating of the heart may be inhibited automatically in responseto the first signal. Beating of the heart may be stimulatedautomatically in response to the second signal. At least one drug may bedelivered during the medical procedure. A nerve may be stimulated toinhibit beating of the heart. Breathing may be stopped while beating ofthe heart is inhibited. Breathing may be stopped automatically.

[0024] The biological characteristic may be a characteristic of blood, acharacteristic of cardiac tissue, a characteristic of a nerve, a fluidflow characteristic, a pressure characteristic, a temperaturecharacteristic, an electrical characteristic, a chemical concentration,a presence of a peptide, a concentration of a peptide, a presence of aprotein, a concentration of a protein, a component of a metabolicprocess, a presence of a gas, a concentration of a gas, a presence ofoxygen, a concentration of a oxygen, a presence of carbon dioxide, aconcentration of carbon dioxide, a chemical characteristic, a physicalcharacteristic, and a physiological characteristic.

[0025] Another aspect of the present invention provides a device forperforming a medical procedure wherein the device includes a processor,a sensor to sense a biological characteristic and at least one nervestimulation electrode. The processor receives a signal from the sensorand adjusts output from the nerve stimulation electrode in response tothe signal.

[0026] The sensor may be an imaging system, an electrical sensor; achemical sensor, an electromagnetic interference sensor, anelectrochemical sensor; a pressure sensor, a sound wave sensor; amagnetic sensor; an ultraviolet sensor; a visible light sensor; aninfrared sensor; a radiation sensor; a flow sensor; a temperaturesensor, a gas sensor, an optical sensor, a pH sensor, a potentiometricsensor, a fluorescence sensor and a biosensor.

[0027] The nerve stimulation electrode may be one or more electrodessuch as endotracheal electrodes, endoesophageal electrodes,intravascular electrodes, transcutaneous electrodes, intracutaneouselectrodes, balloon-type electrodes, basket-type electrodes,umbrella-type electrodes, tape-type electrodes, suction-type electrodes,screw-type electrodes, barb-type electrodes, bipolar electrodes,monopolar electrodes, metal electrodes, wire electrodes, patchelectrodes, cuff electrodes, clip electrodes, needle electrodes andprobe electrodes.

[0028] The device may include a cardiac stimulation electrode tostimulate beating of the heart. The processor receives a signal from thesensor and adjusts output from the cardiac stimulation electrode inresponse to the signal. The cardiac electrode may be, for example, oneor more electrodes such as clip electrodes, needle electrodes, probeelectrodes, pacing electrodes, epicardial electrodes, patch electrodes,intravascular electrodes, balloon-type electrodes, basket-typeelectrodes, tape-type electrodes, umbrella-type electrodes, suction-typeelectrodes, endotracheal electrodes, endoesophageal electrodes,transcutaneous electrodes, intracutaneous electrodes, screw-typeelectrodes, barb-type electrodes, bipolar electrodes, monopolarelectrodes, metal electrodes, wire electrodes and cuff electrodes.

[0029] The device may also include a breathing regulation electrode forcontrolling breathing. The processor adjusts the output from thebreathing regulation electrode in response to the signal. The breathingregulation electrode may be, one or more electrodes such as nervestimulation electrodes, endotracheal electrodes, endoesophagealelectrodes, intravascular electrodes, transcutaneous electrodes,intracutaneous electrodes, balloon-type electrodes, basket-typeelectrodes, umbrella-type electrodes, tape-type electrodes, suction-typeelectrodes, screw-type electrodes, barb-type electrodes, bipolarelectrodes, monopolar electrodes, metal electrodes, wire electrodes,patch electrodes, cuff electrodes, clip electrodes, needle electrodesand probe electrodes.

[0030] The device may also include a drug pump for delivering at leastone drug. The processor adjusts the output of the drug. The drug may be,for example, a beta-blocker, a cholinergic agent, a cholinesteraseinhibitor, a calcium channel blocker, a sodium channel blocker, apotassium channel agent, adenosine, an adenosine receptor agonist, anadenosine deaminase inhibitor, dipyridamole, a monoamine oxidaseinhibitor, digoxin, digitalis, lignocaine, a bradykinin agent, aserotoninergic agonist, an antiarrythmic agent, a cardiac glycoside, alocal anesthetic, atropine, a calcium solution, an agent that promotesheart rate, an agent that promotes heart contractions, dopamine, acatecholamine, an inotrope glucagon, a hormone, forskolin, epinephrine,norepinephrine, thyroid hormone, a phosphodiesterase inhibitor,prostacyclin, prostaglandin and a methylxanthine.

[0031] Another aspect of the present invention provides a system forperforming a medical procedure wherein the system includes a sensor tosense a state of a cardiac tissue and an indicator to indicate the stateof the cardiac tissue. The system may also include a nerve stimulator incommunication with the sensor to inhibit beating of a heart when thestate indicated by the indicator is a non-contracting state. The systemmay also include a cardiac stimulator in communication with the sensorto stimulate beating of a heart when the state indicated by theindicator is a contracting state. The system may also include a drugdelivery means and/or a breathing regulator. The breathing regulator maycontrol a respirator and/or a the breathing regulator may stimulate aphrenic nerve.

[0032] Another aspect of the present invention provides a method forperforming a medical procedure wherein the beating of a heart isinhibited. The medical procedure is performed and a state of cardiactissue is sensed while beating of the heart is inhibited. The beating ofthe heart may be inhibited automatically when the state of cardiactissue is a non-contracting state. A nerve may also be stimulated toinhibit beating of the heart when the state of cardiac tissue is anon-contracting state. Stimulation of the nerve may be stopped when thestate of cardiac contraction is a contracting state. Beating of theheart may be allowed to occur when the state of cardiac tissue is acontracting state. Beating of the heart may also be stimulatedautomatically when the state of cardiac tissue is a contracting state.At least one drug may be delivered during the medical procedure.Breathing may be stopped when the state of cardiac tissue is anon-contracting state.

[0033] Another aspect of the present invention provides a device forperforming a medical procedure wherein the device includes a processor,a sensor to sense a state of cardiac tissue at least one nervestimulation electrode. The processor receives a signal from the sensorand adjusts output from the nerve stimulation electrode in response tothe signal. The device may also include at least one cardiac stimulationelectrode to stimulate beating of the heart. The processor receives asignal from the sensor and adjusts output from the cardiac stimulationelectrode in response to the signal. The device may also include a drugpump for delivering at least one drug and/or a breathing regulationelectrode for controlling breathing. The processor adjusts the output ofthe drug and/or output from the breathing regulation electrode inresponse to a signal.

[0034] Another aspect of the present invention provides a method ofperforming a medical procedure wherein a first vasoactive substance isdelivered to a site of the medical procedure. The medical procedure isthe performed. A second vasoactive substance is then delivered to thesite. The first vasoactive substance may be a vasodilator such as anorganic nitrate, isosorbide mononitrate, a mononitrate, isosorbidedinitrate, a dinitrate, nitroglycerin, a trinitrate, minoxidil, sodiumnitroprusside, hydralazine hydrochloride, nitric oxide, nicardipinehydrochloride, fenoldopam mesylate, diazoxide, enalaprilat, epoprostenolsodium, a prostaglandin, milrinone lactate, a bipyridine, a dopamineD1-like receptor agonist, a dopamine D1-like receptor stimulant and adopamine D1-like receptor activator. The second vasoactive substance maybe a vasoconstrictor such as a sympathomimetic, methoxaminehydrochloride, epinephrine, midodrine hydrochloride, desglymidodrine, analpha-receptor agonist, an alpha-receptor stimulant, and analpha-receptor activator.

[0035] At least one systemic drug such as a beta-blocker, a cholinergicagent, a cholinesterase inhibitor, a calcium channel blocker, a sodiumchannel blocker, a potassium channel agent, adenosine, an adenosinereceptor agonist, an adenosine deaminase inhibitor, dipyridamole, amonoamine oxidase inhibitor, digoxin, digitalis, lignocaine, abradykinin agent, a serotoninergic agonist, an antiarrythmic agent, acardiac glycoside, a local anesthetic, atropine, a calcium solution, anagent that promotes heart rate, an agent that promotes heartcontractions, dopamine, a catecholamine, an inotrope glucagon, ahormone, forskolin, epinephrine, norepinephrine, thyroid hormone, aphosphodiesterase inhibitor, prostacyclin, prostaglandin and amethylxanthine may also be delivered during the procedure. The systemicdrug may be naturally occurring or chemically synthesized.

[0036] A nerve may also be stimulated to adjust the beating of a heartto a first condition. Stimulation of the nerve may be reduced to adjustthe beating of a heart to a second condition.

[0037] Another aspect of the present invention provides a method ofperforming a medical procedure on a vessel of a heart. A nerve isstimulated to adjust the beating of a heart to a first condition. Afirst vasoactive substance is delivered to the vessel. The medicalprocedure is performed an the vessel. A second vasoactive substance isdelivered to the vessel. The heart is stimulated to adjust the beatingof a heart to a second condition. The nerve may be stimulated asubsequent time to re-adjust beating of the heart to the first conditionthe procedure may be continued. The nerve may be a vagal nerve, acarotid sinus nerve, a fat pad. The first vasoactive substance may be avasodilator such as an organic nitrate, isosorbide mononitrate, amononitrate, isosorbide dinitrate, a dinitrate, nitroglycerin, atrinitrate, minoxidil, sodium nitroprusside, hydralazine hydrochloride,nitric oxide, nicardipine hydrochloride, fenoldopam mesylate, diazoxide,enalaprilat, epoprostenol sodium, a prostaglandin, milrinone lactate, abipyridine, a dopamine D1-like receptor agonist, a dopamine D1-likereceptor stimulant and a dopamine D1-like receptor activator. The secondvasoactive substance may be a vasoconstrictor such as a sympathomimetic,methoxamine hydrochloride, epinephrine, midodrine hydrochloride,desglymidodrine, an alpha-receptor

[0038] Another aspect of the present invention provides a method ofharvesting a vessel. A nerve is stimulated to adjust beating of a heartto a first condition. A vasodilative substance is delivered to the heartand the vessel is harvested. A vasoconstrictive substance is thendelivered to the heart and the heart is stimulated to adjust its beatingto a second condition.

[0039] Another aspect of the present invention provides a system forperforming a medical procedure wherein the system includes drug deliverymeans to deliver vasoactive substances to a site of the medicalprocedure, a nerve stimulator in communication with the drug deliverymeans to inhibit beating of a heart and a cardiac stimulator incommunication with the drug delivery means to stimulate beating of theheart. The drug delivery means may be, for example, a spray, a cream, anointment, a medicament, a pill, a patch, a catheter, a cannula, a needleand syringe, a pump, and an iontophoretic drug delivery device. The drugmay be an organic nitrate, isosorbide mononitrate, a mononitrate,isosorbide dinitrate, a dinitrate, nitroglycerin, a trinitrate,minoxidil, sodium nitroprusside, hydralazine hydrochloride, nitricoxide, nicardipine hydrochloride, fenoldopam mesylate, diazoxide,enalaprilat, epoprostenol sodium, a prostaglandin, milrinone lactate, abipyridine, a dopamine D1-like receptor agonist, a dopamine D1-likereceptor stimulant and a dopamine D1-like receptor activator,sympathomimetic, methoxamine hydrochloride, epinephrine, midodrinehydrochloride, desglymidodrine, an alpha-receptor agonist, analpha-receptor stimulant and an alpha-receptor activator. The drug maybe naturally occurring or chemically synthesized.

[0040] Another aspect of the present invention provides a system forperforming a medical procedure wherein the system includes a drugdelivery means to deliver vasoactive substances to a site of the medicalprocedure, a nerve stimulator in communication with the drug deliverymeans to inhibit beating of a heart and a cardiac stimulator incommunication with the drug delivery means to stimulate beating of theheart.

[0041] The drug delivery means may be, for example, a spray, a cream, anointment, a medicament, a pill, a patch, a catheter, a cannula, a needleand syringe, a pump, and an iontophoretic drug delivery device. The drugmay be an organic nitrate, isosorbide mononitrate, a mononitrate,isosorbide dinitrate, a dinitrate, nitroglycerin, a trinitrate,minoxidil, sodium nitroprusside, hydralazine hydrochloride, nitricoxide, nicardipine hydrochloride, fenoldopam mesylate, diazoxide,enalaprilat, epoprostenol sodium, a prostaglandin, milrinone lactate, abipyridine, a dopamine D1-like receptor agonist, a dopamine D1-likereceptor stimulant and a dopamine D1-like receptor activator,sympathomimetic, methoxamine hydrochloride, epinephrine, midodrinehydrochloride, desglymidodrine, an alpha-receptor agonist, analpha-receptor stimulant and an alpha-receptor activator. The drug maybe naturally occurring or chemically synthesized.

[0042] Another aspect of the present invention provides a device fordelivering vasoactive substances during a medical procedure. The deviceincludes a processor, a vasoactive delivery component operativelyconnected to the processor; and a nerve stimulation electrodeoperatively connected to the processor. The processor processes outputfrom the nerve stimulation electrode and automatically deliversvasoactive substances based on output from the nerve stimulationelectrode. The device may also include a cardiac stimulation electrode.The processor processes output from the cardiac stimulation electrodeand automatically delivers vasoactive substances based on output fromthe cardiac stimulation electrode. The device may also include abreathing regulation electrode for controlling breathing. The processoradjusts the output from the breathing regulation electrode. The devicemay also include a drug pump for delivering at least one systemic drug.The processor adjusts the output of the drug.

[0043] The foregoing, and other, features and advantages of theinvention will become further apparent from the following detaileddescription of the presently preferred embodiments, read in conjunctionwith the accompanying drawings. The detailed description and drawingsare merely illustrative of the invention rather than limiting, the scopeof the invention being defined by the appended claims in equivalencethereof.

BRIEF DESCRIPTION OF THE DRAWINGS

[0044]FIG. 1 is a schematic view of one embodiment of a system forperforming a medical procedure in accordance with the present invention;

[0045]FIG. 2 is a schematic view of one embodiment of a system forsensing imminent cardiac contractions during a medical procedure inaccordance with the present invention;

[0046]FIG. 3 is a schematic view of one embodiment of a medical devicein accordance with the present invention;

[0047]FIG. 4 is a schematic view of one embodiment of a medical devicein accordance with the present invention;

[0048]FIG. 5 is a schematic view of one embodiment of a medical devicein accordance with the present invention;

[0049]FIG. 6 is a flow diagram of one embodiment of a method ofperforming a medical procedure in accordance with the present invention;

[0050]FIG. 7 is a flow diagram of one embodiment of a method ofperforming a medical procedure in accordance with the present invention;

[0051]FIG. 8 is a flow diagram of one embodiment of a method ofperforming a medical procedure in accordance with the present invention;

[0052]FIG. 9 is a timeline view of one embodiment of a system forcontrollably stopping or slowing the heart intermittently in a patientmonitoring blood flow in the brain during a medical procedure inaccordance with the present invention;

[0053]FIG. 10 is a timeline view of one embodiment of a system forsensing imminent cardiac contractions during a medical procedure inaccordance with the present invention.

[0054]FIG. 11 is a schematic view of one embodiment of a system fordelivering vasoactive drugs during a medical procedure in accordancewith the present invention;

[0055]FIG. 12 is a schematic view of one embodiment of a medical devicein accordance with the present invention;

[0056]FIG. 13 is a flow diagram of one embodiment of a method ofperforming a medical procedure in accordance with the present invention;and

[0057]FIG. 14 is a timeline view of one embodiment of a system fordelivering vasoactive drugs during a medical procedure in accordancewith the present invention.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

[0058]FIG. 1 shows a schematic view of one embodiment of a system forperforming a medical procedure in accordance with the present inventionat 100. System 100 comprises a nerve stimulator 10, and a cardiacstimulator 20. System 100 may also feature a controller 30 and abreathing regulator 40.

[0059]FIG. 2 shows a schematic view of an alternative embodiment of asystem for performing a medical procedure in accordance with the presentinvention at 100. System 100 comprises a sensor 6, a nerve stimulator10, and a cardiac stimulator 20. System 100 may also feature acontroller 30 and a breathing regulator 40. Sensor 6 may be any suitablesensor, e.g., an electrical sensor, a chemical sensor or a biosensor,for detecting one or more signals indicative of a cardiac contraction orheartbeat. Alternatively, sensor 6 may be any suitable blood gas sensorfor measuring the concentration or saturation of a gas in the bloodstream. For example, sensor 6 may be a sensor for measuring theconcentration or saturation of oxygen or carbon dioxide in the blood.Alternatively, sensor 6 may be any suitable sensor for measuring bloodpressure or flow, for example a Doppler ultrasound sensor system, or asensor for measuring hematocrit (HCT) levels.

[0060] Alternatively, sensor 6 may be a biosensor, for example,comprising an immobilized biocatalyst, enzyme, immunoglobulin,bacterial, mammalian or plant tissue, cell and/or subcellular fractionof a cell. For example, the tip of a biosensor may comprise amitochondrial fraction of a cell, thereby providing the sensor with aspecific biocatalytic activity.

[0061] Sensor 6 may be based on potentiometric technology or fiber optictechnology. For example, the sensor may comprise a potentiometric orfiber optic transducer. An optical sensor may be based on either anabsorbance or fluorescence measurement and may include an UV, a visibleor an IR light source.

[0062] Sensor 6 may be used to detect naturally detectable propertiesrepresentative of one or more characteristics, e.g., chemical, physicalor physiological, of a patient's bodily tissues or fluids. For example,naturally detectable properties of patient's bodily tissues or fluidsmay include pH, fluid flow, electrical current, temperature, pressure,components of metabolic processes, chemical concentrations, for example,the absence or presence of specific peptides, proteins, enzymes, gases,ions, etc.

[0063] Sensor 6 may include one or more imaging systems, camera systemsoperating in UV, visible, or IR range; electrical sensors; voltagesensors; current sensors; piezoelectric sensors; electromagneticinterference (EMI) sensors; photographic plates, polymer-metal sensors;charge-coupled devices (CCDs); photo diode arrays; chemical sensors,electrochemical sensors; pressure sensors, sound wave sensors; magneticsensors; UV light sensors; visible light sensors; IR light sensors;radiation sensors; flow sensors; temperature sensors; or any otherappropriate or suitable sensor. Sensor 5 may be a continuous, in-linemonitoring system or it may be attached to an extracorporeal device.

[0064] In one embodiment of the invention, sensor 6 may be a cerebralblood flow sensor, in which case, the sensor may be placed in anysuitable manner for sensing cerebral blood flow. For example, sensor 6may be inserted between the skull and the dura of the brain.Alternatively, sensor 6 may be placed in the patient's neck. Forexample, at least a portion of sensor 6 may be placed in an artery, suchas the carotid artery. Such a placement would allow measurement of bloodas it flows to the brain. Alternatively, sensor 6 may be placed in avein, such as the jugular vein. This placement would allow measurementof blood as it flows from the brain.

[0065] In the case of blood oxygen saturation sensing, a certain levelof oxygen generally remains in the blood as it flows from the brain.This level may be established by measuring the patient's oxygen prior tosurgery. If blood measured by sensor 6 in the vein has oxygen below theestablished level, the brain is consuming all or most of the oxygenflowing to it and probably requires additional oxygen. Other suitableplacements of sensor 6 may be possible. Sensor 6 may be used to alert asurgeon to changes in the patient's circulatory system.

[0066] In one embodiment of the present invention, nerve stimulator 10may be used to electrically manipulate cardiac rhythm by stimulating thevagus nerve. This vagal stimulation may produce asystole (slowing orstopping of the heart's beating.) Once this induced asystole is stopped,i.e. once the vagal stimulation is stopped, the heart may be allowed toreturn to its usual cardiac rhythm. Alternatively, the heart may bepaced with an electrical pacing system, thereby maintaining a normalcardiac output. Vagal stimulation, alone or in combination withelectrical pacing, may be used selectively and intermittently to allow asurgeon to perform a medical procedure during intermittent periods ofasystole.

[0067] It is known that stimulation of the vagus nerve can reduce thesinus rate, as well as prolong AV conduction time or, if stimulationenergies are high enough, induce AV node block. Use of vagal nervestimulation to treat supraventricular arrhythmias and angina pectoris isdisclosed in the article “Vagal Tuning” by Bilgutay et al., Journal ofThoracic and Cardiovascular Surgery, Vol. 56, No. 1, July, 1968, pp.71-82. It is also known that stimulation of the carotid sinus nerveproduces a similar result, as disclosed in the article “Carotid SinusNerve Stimulation in the Treatment of Angina Pectoris andSupraventricular Tachycardia” by Braunwald et al., published inCalifornia Medicine, Vol. 112, pp. 41-50, March, 1970.

[0068] As set forth in “Functional Anatomy of the Cardiac EfferentInnervation” by Randall et al., in Neurocardiology, edited by Kulbertuset al, Futura Publishing Co., 1988, direct surgical excision of the fatpad associated with the SA node affects the functioning of the SA nodewithout significantly affecting the AV node. Similarly, excision of thefat pad associated with the AV node affects functioning of the AV nodewithout significantly affecting the SA node.

[0069] As set forth in the article “Parasympathetic PostganglionicPathways to the Sinoatrial Node”, Bluemel et al., Am. J. Physiol. 259,(Heart Circ. Physiol. 28) H1504-H1510, 1990, stimulation of the fat padassociated with the SA node results in slowing of the sinus rate withoutthe accompanying prolongation of AV conduction time which normallyresults from vagal nerve stimulation. The article also indicates thatstimulation of the fat pad associated with the AV node is believed toproduce corresponding effects limited to the AV node, i.e., extension ofthe AV conduction time without concurrent slowing of the sinus rate.

[0070] As set forth in the article “Neural Effects on Sinus Rate andAtrial Ventricular Conduction Produced by Electrical Stimulation From aTransvenous Electrode Catheter in the Canine Right Pulmonary Artery” byCooper et al., published in Circulation Research, Vol. 46, No. 1,January, 1980, pp. 48-57, the fat pads associated with both the AV nodeand the SA node may be stimulated by means of electrodes located in theright pulmonary artery. The results obtained include both a depressionof the sinus rate and a prolongation of the AV conduction time inresponse to continuous stimulation at 2-80 Hz at up to 50 ma.

[0071] Generally in healthy individuals, the SA node functions as thepacemaker. Normal heart rhythm associated with the SA node is typicallyreferred to as sinus rhythm. When the SA node fails, the AV nodegenerally takes over creating a heart rate of approximately 35 to 60beats per minute. Heart rhythm associated with the AV node is typicallyreferred to as nodal rhythm. When the AV node itself is blocked orinjured, a new even slower pacemaker site may form at the junction ofthe AV node and the His bundle. Heart rhythm associated with thisjunction is typically referred to as junctional escape rhythm. When thisjunction site is inhibited, the Purkinje fibers in the His bundle orbelow may act as a pacemaker creating a heart rate of approximately 30beats per minute. Heart rhythm associated with the Purkinje fibers istypically referred to as idioventricular rhythm.

[0072] In one embodiment of the present invention, nerve stimulator 10may be used to electrically manipulate cardiac rhythm by stimulating thecarotid sinus nerve, the fat pad associated with the SA node, the fatpad associated with the AV node, the junction of the AV node and the Hisbundle and/or the Purkinje fibers.

[0073] In one embodiment of the present invention, nerve stimulator 10is used alone or in combination with other heart rate inhibiting agentsto temporarily stop or slow the beating heart, thereby eliminating orreducing heart motion and/or blood flow during a medical procedure. Forexample, the present invention may be used to eliminate or reduce motionin the anastomosis field during CABG procedures such that a facilitatedanastomosis procedure may be performed safely and effectively. Thenumber of occasions that the vagal nerve may be stimulated depends onthe type of medical procedure to be performed. Likewise, the type ofmedical procedure to be performed will dictate the duration of theindividual electrical stimulations.

[0074] Nerve stimulator 10 may be powered by AC current, DC current orit may be battery powered by a disposable or re-chargeable battery.Nerve stimulator 10 may be configured to synchronize activation anddeactivation of breathing regulator 40 with vagal stimulation, therebyminimizing or eliminating unwanted heart and chest motion associatedwith the patient's breathing. Nerve stimulator 10 may comprise a surgeoncontrolled switch box. A switch may be incorporated in or on one of thesurgeon's instruments, such as surgical site retractor, or any otherlocation easily and quickly accessed by the surgeon for regulation ofthe nerve stimulator 10 by the surgeon. The switch may be, for example,a hand switch, a foot switch, or a voice-activated switch comprisingvoice-recognition technologies.

[0075] A visual and/or audible signal used to alert a surgeon to thecompletion or resumption of vagal nerve stimulation may be incorporatedinto nerve stimulator 10. For example, a beeping tone or flashing lightthat increases in frequency as the nerve stimulation period should endor begin may be used.

[0076] Nerve stimulator 10 may be slaved to cardiac stimulator 20 orcardiac stimulator 20 may be slaved to nerve stimulator 10. For example,the output of cardiac stimulator 20 may be off whenever the output ofnerve stimulator 10 is on. Software controlling cardiac stimulator 20may be designed to automatically commence cardiac pacing if the heartdoes not resume beating within a pre-determined interval after cessationof vagal nerve stimulation. In addition, the software controlling nervestimulator 10 may be designed to automatically stop vagal nervestimulation if the heart has been stopped for too long. For example, apredetermined time interval may be set to automatically stop vagalstimulation. In one embodiment of the invention, if sensor 6 of thepresent invention indicates that not enough blood is flowing to thebrain, vagal stimulation may be stopped, thereby allowing the heart tobeat again.

[0077] In one embodiment of the present invention, cardiac stimulator 20may be used to stimulate the heart as desired. For example in oneembodiment of the present invention, sensor 6 may indicate that notenough blood is flowing to the brain causing nerve stimulator 10 to beautomatically turned off and cardiac stimulator 20 to be automaticallyturned on. Alternatively, the surgeon may turn on cardiac stimulator 20to begin stimulation. As with nerve stimulator 10, cardiac stimulator 20may be intermittently stopped and started to allow the surgeon toperform individual steps of a medical procedure.

[0078] Cardiac stimulator 20 may be a conventional ventricular demandpacer or dual chamber (atrial-ventricular) pacer. Cardiac stimulator 20may be powered by AC current, DC current or it may be battery poweredeither by a disposable or re-chargeable battery. Cardiac stimulator 20may be configured to synchronize activation and deactivation ofbreathing regulator 40 with pacing, thereby minimizing or eliminatingunwanted heart and chest motion associated with the patient's breathing.Cardiac stimulator 20 may be any conventional pacing device suitable forventricular demand pacing and having leads electrically coupled to aswitch box. Cardiac stimulator 20 may be combined in a single unit witha switch box. Cardiac stimulator 20 may comprise a surgeon controlledswitch box. A switch may be incorporated in or on one of the surgeon'sinstruments, such as surgical site retractor, or any other locationeasily and quickly accessed by the surgeon for regulation of the cardiacstimulator by the surgeon. The switch may be, for example, a handswitch, a foot switch, or a voice-activated switch comprisingvoice-recognition technologies. A single switch may be used to regulateboth cardiac stimulator 20 and nerve stimulator 10.

[0079] A visual and/or audible signal used to prepare a surgeon for theresumption of pacing may be incorporated into cardiac stimulator 20. Forexample, a beeping tone or flashing light that increases in frequency asthe pacing period ends may be used. A single signaling method or devicemay be used for both cardiac stimulator 20 and nerve stimulator 10.

[0080] Nerve stimulator 10 and/or cardiac stimulator 20 may be slaved toa robotic system or a robotic system may be slaved to nerve stimulator10 and/or cardiac stimulator 20. Breathing regulator 40 and/or sensor 6and other components may also be slaved to such a system or the systemmay be slaved to breathing regulator 40 and/or sensor 6 and/or othercomponents. Computer- and voice-controlled robotic systems that positionand maneuver endoscopes and/or other surgical instruments for performingmicrosurgical procedures such as anastomoses through small incisions maybe used by a surgeon to perform precise and delicate maneuvers. Theserobotic systems may allow a surgeon to perform a variety ofmicrosurgical procedures including endoscopic CABG. Endoscopic CABG mayallow multiple occluded coronary arteries to be bypassed without athoracotomy or mini-thoracotomy. Heart valve repair and replacement mayalso be other surgical applications for these robotic systems. Ingeneral, robotic systems may include head-mounted displays whichintegrate 3-D visualization of surgical anatomy and related diagnosticand monitoring data, miniature high resolution 2-D and 3-D digitalcameras, a computer, a high power light source and a standard videomonitor.

[0081] In one embodiment of the present invention, breathing regulator40 may be used to stimulate the phrenic nerve in order to provide adiaphragmatic pacemaker. Breathing regulator 40 may comprise one or moreelectrodes for supplying electrical current to the phrenic nerve tocontrol breathing during vagal and/or cardiac stimulation and/ordestimulation. Electrodes used to stimulate the phrenic nerve may be,for example, non-invasive, e.g., clips, or invasive, e.g., needles orprobes. The application of an electrical stimulus to the phrenic nervemay include, but is not limited to bipolar and/or monopolar techniques.Different electrode positions are accessible through various accessopenings, for example, in the cervical or thorax regions. Nervestimulation electrodes may be positioned through a thoracotomy,sternotomy, endoscopically through a percutaneous port, through a stabwound or puncture, through a small incision, placed on the skin or incombinations thereof. The present invention may include variouselectrodes, catheters and electrode catheters suitable for phrenic nervestimulation to control breathing.

[0082] Phrenic nerve stimulation electrodes may be intravascular,patch-type, balloon-type, basket-type, umbrella-type, tape-type,cuff-type, suction-type, screw-type, barb-type, bipolar, monopolar,metal, wire, endotracheal, endoesophageal, intravascular, transcutaneousor intracutaneous electrodes. Guided or steerable catheter devicescomprising electrodes may be used alone or in combination with the nervestimulation electrodes. For example, a catheter comprising one or morewire, metal strips or metal foil electrodes or electrode arrays may beused. The catheter may comprise, for example, a balloon which may beinflated with air or liquid to press the electrodes firmly against avessel wall that lays adjacent the phrenic nerve.

[0083] Phrenic nerve stimulation electrodes may be oriented in anyfashion along the catheter device, including longitudinally ortransversely. Various techniques such as ultrasound, fluoroscopy andechocardiography may be used to facilitate positioning of theelectrodes. If desired or necessary, avoidance of obstruction of bloodflow may be achieved with notched catheter designs or with catheterswhich incorporate one or more tunnels or passageways.

[0084] In another embodiment of the present invention, breathingregulator 40 may comprise a connector which interfaces with a patient'srespirator, and sends a logic signal to activate or deactivate therespirator to control breathing during vagal and/or cardiac stimulationand/or destimulation.

[0085]FIG. 3 shows one embodiment of the present invention at 200. Inthis embodiment, the elements named above may be combined or connectedto a control unit along with other components. The unit 200 may be usedto coordinate the various elements. Unit 200 may incorporate acontroller or any suitable processor 230.

[0086] Unit 200 may incorporate a nerve stimulator. For example, FIG. 3shows an electrode for nerve stimulation at 210. Electrodes used tostimulate a nerve such as the vagal nerve may be, for example,non-invasive, e.g., clips, or invasive, e.g., needles or probes. Theapplication of an electrical stimulus to the right or left vagal nervemay include, but is not limited to bipolar and/or monopolar techniques.Different electrode positions are accessible through various accessopenings, for example, in the cervical or thorax regions. Nervestimulation electrodes 210 may be positioned through a thoracotomy,sternotomy, endoscopically through a percutaneous port, through a stabwound or puncture, through a small incision in the neck or chest,through the internal jugular vein, the esophagus, the trachea, placed onthe skin or in combinations thereof. Electrical stimulation may becarried out on the right vagal nerve, the left vagal nerve or to bothnerves simultaneously or sequentially. The present invention may includevarious electrodes, catheters and electrode catheters suitable for vagalnerve stimulation to temporarily stop or slow the beating heart alone orin combination with other heart rate inhibiting agents.

[0087] Nerve stimulation electrodes 210 may be endotracheal,endoesophageal, intravascular, transcutaneous, intracutaneous,patch-type, balloon-type, cuff-type, basket-type, umbrella-type,tape-type, screw-type, barb-type, metal, wire or suction-typeelectrodes. Guided or steerable catheter devices comprising electrodesmay be used alone or in combination with the nerve stimulationelectrodes 210. For example, a catheter comprising one or more wire,metal strips or metal foil electrodes or electrode arrays may beinserted into the internal jugular vein to make electrical contact withthe wall of the internal jugular vein, and thus stimulate the vagalnerve adjacent to the internal jugular vein. Access to the internaljugular vein may be via, for example, the right atrium, the right atrialappendage, the inferior vena cava or the superior vena cava. Thecatheter may comprise, for example, a balloon which may be inflated withair or liquid to press the electrodes firmly against the vessel wall.Similar techniques may be performed by insertion of a catheter-typedevice into the trachea or esophagus. Additionally, tracheal tubes andesophageal tubes comprising electrodes may be used.

[0088] Nerve stimulation electrodes 210 may be oriented in any fashionalong the catheter device, including longitudinally or transversely.Various techniques such as ultrasound, fluoroscopy and echocardiographymay be used to facilitate positioning of the electrodes. If desired ornecessary, avoidance of obstruction of blood flow may be achieved withnotched catheter designs or with catheters which incorporate one or moretunnels or passageways.

[0089] In one embodiment of the present invention, the location of theelectrodes 210 is chosen to elicit maximum bradycardia effectivenesswhile minimizing current spread to adjacent tissues and vessels and toprevent the induction of post stimulation tachycardia. Furthermore, anon-conductive material such as plastic may be employed to sufficientlyenclose the electrodes of all the configurations to shield them from thesurrounding tissues and vessels, while exposing their confronting edgesand surfaces for positive contact with the vagal nerve or selectedtissues.

[0090] Unit 200 may also incorporate a cardiac stimulator. For example,FIG. 2 shows an electrode for stimulation of the heart at 220. Cardiacelectrodes 220 used to stimulate the heart may be, for example,non-invasive, e.g., clips, or invasive, e.g., needles or probes.Electrodes 220 may be positioned through a thoracotomy, sternotomy,endoscopically through a percutaneous port, through a stab wound orpuncture, through a small incision in the chest, placed on the chest orin combinations thereof. The present invention may also use variouselectrodes, catheters and electrode catheters suitable for pacing theheart, e.g., epicardial, patch-type, intravascular, balloon-type,basket-type, umbrella-type, tape-type electrodes, suction-type, pacingelectrodes, endotracheal electrodes, endoesophageal electrodes,transcutaneous electrodes, intracutaneous electrodes, screw-typeelectrodes, barb-type electrodes, bipolar electrodes, monopolarelectrodes, metal electrodes, wire electrodes and cuff electrodes.Guided or steerable catheter devices comprising electrodes may be usedalone or in combination with the electrodes.

[0091] Controller 230 may be used to gather information from nervestimulation electrodes 210 and cardiac stimulation electrodes 220.Controller 230 may also be used to control the stimulation levels andstimulation duration of nerve stimulation electrodes 210 and cardiacstimulation electrodes 220. Controller 230 may also gather and processinformation from the various components of the system, e.g., sensor 6.This information may be used to adjust stimulation levels andstimulation times of nerve stimulation electrodes 210 and cardiacstimulation electrodes 220.

[0092] Unit 200 may incorporate one or more switches to facilitateregulation of the various components by the surgeon. One example of sucha switch is shown as foot pedal 250. The switch may also be, forexample, a hand switch, or a voice-activated switch comprisingvoice-recognition technologies. The switch may be incorporated in or onone of the surgeon's instruments, such as surgical site retractor, orany other location easily and quickly accessed by the surgeon.

[0093] Unit 200 may also include a display 260. Unit 200 may alsoinclude other means of indicating the status of various components tothe surgeon such as a numerical display, gauges, a monitor display oraudio feedback. Unit 200 may also include one or more visual and/oraudible signals used to prepare a surgeon for the start or stop of nervestimulation and/or cardiac stimulation.

[0094]FIG. 4 shows one embodiment of the present invention whereinsensor 6 may comprise a cardiac contraction sensor 206 incorporated withcontrol unit 200. In this embodiment, the elements named above may becombined or connected to control unit 200 along with other components.Control unit 200 may be used to coordinate the various elements.

[0095] As shown in FIG. 4, sensor 206 may be a monitor for mounting onor near the heart during surgery. Such a monitor may monitor theelectrical activity of the heart by picking up and amplifying electricalsignals from the heart and displaying an output. For example, the outputmay be displayed on display 216. The surgeon may check this outputperiodically to see if the output reaches a level that indicates anescape beat is probable. Alternatively, the monitor may be programmed toindicate by a signal, such as an audio or visual signal, that theelectrical activity has reached a predetermined level that is indicativeof an imminent escape beat.

[0096] Unit 200 may include display 270 in addition to display 216 orinstead of display 216. Unit 200 may include other means of indicatingto the surgeon such as a numerical display, gauges, a monitor display oraudio feedback that the electrical activity has reached a predeterminedlevel that is indicative of an imminent escape beat. Unit 200 may alsoinclude one or more visual and/or audible signals used to prepare asurgeon of an imminent escape beat.

[0097] Cardiac contraction sensor 206 may be a sensor that detectscardiac depolarizations. The electrical signal generated by the sinusnode of the heart causes the atria to contract to force blood into theventricles. After a brief delay, the ventricles contract to force bloodout through the body. The contraction of the ventricles is reflected bythe passage of a depolarization wavefront through the heart muscle. If adepolarization is sensed, an escape beat is likely to occur. One suchdepolarization sensor is disclosed in U.S. Pat. No. 5,156,149 entitled“Sensor for Detecting Cardiac Depolarizations Particularly Adapted foruse in a Cardiac Pacemaker”, Oct. 2, 1992, to inventor Hudrlik. Thispatent is assigned to Medtronic, Inc. and is incorporated herein byreference.

[0098] Cardiac contraction sensor 206 may be coupled to cardiacstimulator 20. Such a sensor may detect the response of tissue near thestimulator 20. If the tissue is stimulated during the procedure bystimulator 20, the cardiac stimulation may cause an escape beat evenafter stimulation has been reduced or stopped, particularly if cardiacstimulation is only reduced during the procedure rather than fullystopped. One such detector is disclosed in U.S. Pat. No. 5,265,603entitled “Electronic Capture Detection for a Pacer,” Nov. 30, 1993, toinventor Hudrlik. This patent is assigned to Medtronic, Inc. and isincorporated herein by reference.

[0099] Cardiac contraction sensor 206 may be an apparatus that sensespower levels of depolarizations in heart tissue. Such a sensor may beused to distinguish between normally conducted and ectopic heart beatswhile the heart is beating or may be used to sense an imminent heartbeat while the heart is slowed or substantially stilled during a medicalprocedure. One apparatus that may serve as such a sensor is disclosed inU.S. Pat. No. 5,411,529 entitled “Waveform Discriminator for CardiacStimulation Devices”, May 2, 1995, to inventor Hurdlik. This patent isassigned to Medtronic, Inc. and is incorporated herein by reference.

[0100] Other suitable sensors may also serve as cardiac contractionsensor 206. Sensor 206 may be or may incorporate one or more sensingelectrodes 226. Sensing electrodes 226 incorporated with sensor 206 maybe, for example, non-invasive, e.g., clips, or invasive, e.g., needlesor probes. Electrodes 226 may be positioned through a thoracotomy,sternotomy, endoscopically through a percutaneous port, through a stabwound or puncture, through a small incision in the chest, placed on thechest or in combinations thereof. The present invention may also usevarious electrodes, catheters and electrode catheters, e.g., epicardial,patch-type, intravascular, balloon-type, basket-type, umbrella-type,tape-type electrodes, suction-type, pacing electrodes, endotrachealelectrodes, endoesophageal electrodes, transcutaneous electrodes,intracutaneous electrodes, screw-type electrodes, barb-type electrodes,bipolar electrodes, monopolar electrodes, metal electrodes, wireelectrodes and cuff electrodes. Guided or steerable catheter devicescomprising electrodes may be used alone or in combination with theelectrodes. Although FIG. 4 shows a separate sensor 206 and cardiacstimulator 220, one sensing/stimulating electrode may serve bothfunctions in one embodiment of the invention.

[0101] All or a portion of cardiac contraction sensor 206 may be placedin any suitable manner for sensing an imminent cardiac contraction. Forexample, sensor 206 may incorporate a lead as shown at 226, which may beused to attach the sensor to the heart. The lead may also be used tomonitor electrical signals of the heart as described above. Sensor 206may be placed in any suitable area of the heart. For example, sensor 206may be placed near the location of the cardiac stimulator 220 asdescribed above. Sensor 206 may be placed near the right ventricle, theleft ventricle, the right atrium, or the left atrium. Other suitableplacements of the sensor 206 may be possible. The sensor's optimallocation will depend primarily on the sensor's mode of operation.

[0102]FIG. 5 shows one embodiment of the present invention whereinsensor 6 may comprise a blood sensor 205 incorporated with control unit200. In this embodiment, the elements named above may be combined orconnected to a control unit along with other components. Unit 200 may beused to coordinate the various elements. Unit 200 may incorporate acontroller as described above or any suitable processor 230. Forexample, the processor may process sensed blood information from sensor205. The controller may store and/or process such information before,during and/or after a medical procedure. For example, the patient'soxygen concentration or blood pressure may be sensed, stored andprocessed prior to and during surgery. Unit 200 may include display 270for displaying sensed blood information from sensor 205. Unit 200 mayalso include other means of indicating the status of various componentsto the surgeon such as a numerical display, gauges, a monitor display oraudio feedback. Unit 200 may also include one or more visual and/oraudible signals used to prepare a surgeon for the start or stop of nervestimulation and/or cardiac stimulation.

[0103]FIG. 6 shows a flow diagram of one embodiment of the presentinvention. The patient is prepared for a medical procedure at 500.

[0104] At block 510, a nerve that controls the beating of the heart isstimulated. Such a nerve may be for example a vagal nerve. During thistime, one or more of a variety of pharmacological agents or drugs may bedelivered. These drugs may produce reversible asystole of a heart whilemaintaining the ability of the heart to be electrically paced. Otherdrugs may be administered for a variety of functions and purposes asdescribed below. Drugs delivered may be administered at the beginning ofthe procedure, intermittently during the procedure, continuously duringthe procedure, or following the procedure. At Block 520, a medicalprocedure may be performed or begun. Such a procedure may be for examplesurgery on the heart. Alternatively, the procedure may be surgeryperformed on another organ of the body.

[0105] After a time, the medical procedure or one phase of the procedureis completed at 520. After some phase of the medical procedure isperformed, cardiac contractions are allowed to occur (Block 530) Cardiaccontractions may need to occur intermittently during the procedure toensure adequate blood flow. In one embodiment, the stimulation from thenerve stimulator 10 is stopped or slowed enough to allow the heart tocontract. For example, the vagal nerve stimulation is removed, therebyallowing cardiac contractions to occur.

[0106] In one embodiment of the present invention, the heart may bestimulated to ensure that cardiac contractions occur (Block 535). Forexample, cardiac stimulator 20 may be used to apply pacing pulses to theheart to encourage the heart to contract normally. In particular, thepacing pulses may be applied to the ventricle as is well known in thefield.

[0107] The present invention permits the heat to be stilled for selectedand controllable periods of time in order to permit cardiac or othermedical procedure to be performed. While such a period of stillness isdesired, it must not last too long, otherwise insufficient blood andoxygen is delivered to organs. Thus, it is necessary to have the periodswhen the heart is beating (Blocks 530, 535).

[0108] If additional medical procedures or additional stages of medicalprocedures need to be performed, the heart may again be stilled usingthe methods of stilling the heart described above. Therefore from Block530 or Block 535, the method may be repeated at 540. For example, theheart may again be prevented from contracting by stimulation of thevagal nerve (Block 510). Additional drugs may be delivered or the drugspreviously administered may continue to be administered.

[0109] Additional surgery, additional steps in the medical procedure oradditional medical procedures may again be performed (Block 520) whilethe heart is still. Then, this stage of stillness may be followed byanother stage when the stimulation is removed (Block 530) and the heartis allowed to contract. Again, the heart may be stimulated to encouragecontractions (Block 535).

[0110] This cycle may be repeated until the procedure, such as thesurgery, is completed. After the procedure is completed, step 535 may beperformed until the heart is beating normally. At the procedure's end,one or more of a variety of pharmacological agents or drugs may bedelivered or may continue to be delivered for example to alleviate painor aid in recuperation. Other drugs may be administered for a variety offunctions and purposes as described above.

[0111] For example, a surgical procedure at 520 may require severalstitches to be made by the surgeon. The surgeon may stimulate the vagalnerve at 510 to stop the heart. Then the surgeon may make the firststitch at 520. The surgeon may then reduce or halt stimulation at 530and allow the heart to contract. The surgeon may also pace the heart at535. Then at 540, the surgeon may return to 510 to inhibit contractionsof the heart. At 520, the surgeon will then make the second stitch. Thisprocess may be repeated (the loop designated by 540 may be repeated)until all the required stitches have been made.

[0112]FIG. 7 shows a flow diagram of one embodiment of the presentinvention. The patient is prepared for a medical procedure at 500. Inone embodiment of the invention, the patient's initial heart rate may bemeasured (Block 505). This initial reading is then used as a gauge tocompare with the electrical signals detected by sensor 6 during theprocedure. In one embodiment, the sensor alerts the surgeon if thesensed electrical (or depolarization) signals reach a predeterminedlevel.

[0113] At Block 510, a nerve that controls the beating of the heart isstimulated. Such a nerve may be for example a vagal nerve. At Block 510,one or more of a variety of pharmacological agents or drugs may bedelivered. These drugs may produce reversible asystole of a heart whilemaintaining the ability of the heart to be electrically paced. Otherdrugs may be administered for a variety of functions and purposes asdescribed below. Drugs delivered during the medical procedure may beadministered at the beginning of the procedure, intermittently duringthe procedure, continuously during the procedure or following theprocedure.

[0114] Drugs, drug formulations or compositions suitable foradministration to a patient during a medical procedure may include apharmaceutically acceptable carrier or solution in an appropriatedosage. There are a number of pharmaceutically acceptable carriers thatmay be used for delivery of various drugs, for example, via directinjection, oral delivery, suppository delivery, transdermal delivery,epicardial delivery and/or inhalation delivery. Pharmaceuticallyacceptable carriers include a number of solutions, preferably sterile,for example, water, saline, Ringer's solution and/or sugar solutionssuch as dextrose in water or saline. Other possible carriers that may beused include sodium citrate, citric acid, amino acids, lactate,mannitol, maltose, glycerol, sucrose, ammonium chloride, sodiumchloride, potassium chloride, calcium chloride, sodium lactate, and/orsodium bicarbonate. Carrier solutions may or may not be buffered.

[0115] Drug formulations or compositions may include antioxidants orpreservatives such as ascorbic acid. They may also be in apharmaceutically acceptable form for parenteral administration, forexample to the cardiovascular system, or directly to the heart, such asintracoronary infusion or injection. Drug formulations or compositionsmay comprise agents that provide a synergistic effect when administeredtogether. A synergistic effect between two or more drugs or agents mayreduce the amount that normally is required for therapeutic delivery ofan individual drug or agent. Two or more drugs may be administered, forexample, sequentially or simultaneously. Drugs may be administered viaone or more bolus injections and/or infusions or combinations thereof.The injections and/or infusions may be continuous or intermittent. Drugsmay be administered, for example, systemically or locally, for example,to the heart, to a coronary artery and/or vein, to a pulmonary arteryand/or vein, to the right atrium and/or ventricle, to the left atriumand/or ventricle, to the aorta, to the AV node, to the SA node, to anerve and/or to the coronary sinus. Drugs may be administered ordelivered via intravenous, intracoronary and/or intraventricularadministration in a suitable carrier. Examples of arteries that may beused to deliver drugs to the AV node include the AV node artery, theright coronary artery, the right descending coronary artery, the leftcoronary artery, the left anterior descending coronary artery andKugel's artery. Drugs may be delivered systemically, for example, viaoral, transdermal, intranasal, suppository or inhalation methods. Drugsalso may be delivered via a pill, a spray, a cream, an ointment or amedicament formulation.

[0116] Drugs may be delivered via a drug delivery device that maycomprise a catheter, such as a drug delivery catheter or a guidecatheter, a patch, such as a transepicardial patch that slowly releasesdrugs directly into the myocardium, a cannula, a pump and/or ahypodermic needle and syringe assembly. A drug delivery catheter mayinclude an expandable member, e.g., a low-pressure balloon, and a shafthaving a distal portion, wherein the expandable member is disposed alongthe distal portion. A catheter for drug delivery may comprise one ormore lumens and may be delivered endovascularly via insertion into ablood vessel, e.g., an artery such as a femoral, radial, subclavian orcoronary artery. The catheter can be guided into a desired positionusing various guidance techniques, e.g., flouroscopic guidance and/or aguiding catheter or guide wire techniques.

[0117] Drugs may be delivered via an iontophoretic drug delivery deviceplaced on the heart. In general, the delivery of ionized drugs may beenhanced via a small current applied across two electrodes. Positiveions may be introduced into the tissues from the positive pole, ornegative ions from the negative pole. The use of iontophoresis maymarkedly facilitate the transport of certain ionized drug molecules. Forexample, lidocaine hydrochloride may be applied to the heart via a drugpatch comprising the drug. A positive electrode could be placed over thepatch and current passed. The negative electrode would contact the heartor other body part at some desired distance point to complete thecircuit. One or more of the electrodes may also be used as nervestimulation electrodes 210, as cardiac stimulation electrodes 220 or assensing electrodes 226.

[0118] The two divisions of the autonomic nervous system that regulatethe heart have opposite functions. First, the adrenergic or sympatheticnervous system increases heart rate by releasing epinephrine andnorepinephrine. Second, the parasympathetic system also known as thecholinergic nervous system or the vagal nervous system decreases heartrate by releasing acetylcholine. Catecholamines such as norepinephrine(also called noradrenaline) and epinephrine (also called adrenaline) areagonists for beta-adrenergic receptors. An agonist is a stimulantbiomolecule or agent that binds to a receptor.

[0119] Beta-adrenergic receptor blocking agents compete withbeta-adrenergic receptor stimulating agents for available beta-receptorsites. When access to beta-receptor sites are blocked by receptorblocking agents, also known as beta-adrenergic blockade, thechronotropic or heart rate, inotropic or contractility, and vasodilatorresponses to receptor stimulating agents are decreased proportionately.Therefore, beta-adrenergic receptor blocking agents are agents that arecapable of blocking beta-adrenergic receptor sites.

[0120] Since beta-adrenergic receptors are concerned with contractilityand heart rate, stimulation of beta-adrenergic receptors, in general,increases heart rate, the contractility of the heart and the rate ofconduction of electrical impulses through the AV node and the conductionsystem.

[0121] Drugs, drug formulations and/or drug compositions that may beused according to this invention may include any naturally occurring orchemically synthesized (synthetic analogues) beta-adrenergic receptorblocking agents. Beta-adrenergic receptor blocking agents or□-adrenergic blocking agents are also known as beta-blockers or□-blockers and as class II antiarrhythmics.

[0122] The term “beta-blocker” appearing herein may refer to one or moreagents that antagonize the effects of beta-stimulating catecholamines byblocking the catecholamines from binding to the beta-receptors. Examplesof beta-blockers include, but are not limited to, acebutolol,alprenolol, atenolol, betantolol, betaxolol, bevantolol, bisoprolol,carterolol, celiprolol, chlorthalidone, esmolol, labetalol, metoprolol,nadolol, penbutolol, pindolol, propranolol, oxprenolol, sotalol,teratolo, timolol and combinations, mixtures and/or salts thereof.

[0123] The effects of administered beta-blockers may be reversed byadministration of beta-receptor agonists, e.g., dobutamine orisoproterenol.

[0124] The parasympathetic or cholinergic system participates in controlof heart rate via the sinoatrial (SA) node, where it reduces heart rate.Other cholinergic effects include inhibition of the AV node and aninhibitory effect on contractile force. The cholinergic system actsthrough the vagal nerve to release acetylcholine, which, in turn,stimulates cholinergic receptors. Cholinergic receptors are also knownas muscarinic receptors. Stimulation of the cholinergic receptorsdecreases the formation of cAMP. Stimulation of cholinergic receptorsgenerally has an opposite effect on heart rate compared to stimulationof beta-adrenergic receptors. For example, beta-adrenergic stimulationincreases heart rate, whereas cholinergic stimulation decreases it. Whenvagal tone is high and adrenergic tone is low, there is a marked slowingof the heart (sinus bradycardia). Acetylcholine effectively reduces theamplitude, rate of increase and duration of the SA node actionpotential. During vagal nerve stimulation, the SA node does not arrest.Rather, pacemaker function may shift to cells that fire at a slowerrate. In addition, acetylcholine may help open certain potassiumchannels thereby creating an outward flow of potassium ions andhyperpolarization. Acetylcholine also slows conduction through the AVnode.

[0125] Drugs, drug formulations and/or drug compositions that may beused according to this invention may include any naturally occurring orchemically synthesized (synthetic analogues) cholinergic agent. The term“cholinergic agent” appearing herein may refer to one or morecholinergic receptor modulators or agonists. Examples of cholinergicagents include, but are not limited to, acetylcholine, carbachol(carbamyl choline chloride), bethanechol, methacholine, arecoline,norarecoline and combinations, mixtures and/or salts thereof.

[0126] Drugs, drug formulations and/or drug compositions that may beused according to this invention may include any naturally occurring orchemically synthesized cholinesterase inhibitor. The term“cholinesterase inhibitor” appearing herein may refer to one or moreagents that prolong the action of acetylcholine by inhibiting itsdestruction or hydrolysis by cholinesterase. Cholinesterase inhibitorsare also known as acetylcholinesterase inhibitors. Examples ofcholinesterase inhibitors include, but are not limited to, edrophonium,neostigmine, neostigmine methylsulfate, pyridostigmine, tacrine andcombinations, mixtures and/or salts thereof.

[0127] There are ion-selective channels within certain cell membranes.These ion selective channels include calcium channels, sodium channelsand/or potassium channels. Therefore, other drugs, drug formulationsand/or drug compositions that may be used according to this inventionmay include any naturally occurring or chemically synthesized calciumchannel blocker. Calcium channel blockers inhibit the inward flux ofcalcium ions across cell membranes of arterial smooth muscle cells andmyocardial cells. Therefore, the term “calcium channel blocker”appearing herein may refer to one or more agents that inhibit or blockthe flow of calcium ions across a cell membrane. The calcium channel isgenerally concerned with the triggering of the contractile cycle.Calcium channel blockers are also known as calcium ion influxinhibitors, slow channel blockers, calcium ion antagonists, calciumchannel antagonist drugs and as class IV antiarrhythmics. A commonlyused calcium channel blocker is verapamil.

[0128] Administration of a calcium channel blocker, e.g., verapamil,generally prolongs the effective refractory period within the AV nodeand slows AV conduction in a rate-related manner, since the electricalactivity through the AV node depends significantly upon the influx ofcalcium ions through the slow channel. A calcium channel blocker has theability to slow a patient's heart rate, as well as produce AV block.Examples of calcium channel blockers include, but are not limited to,amiloride, amlodipine, bepridil, diltiazem, felodipine, isradipine,mibefradil, nicardipine, nifedipine (dihydropyridines), nickel,nimodinpine, nisoldipine, nitric oxide (NO), norverapamil and verapamiland combinations, mixtures and/or salts thereof. Verapamil and diltiazemare very effective at inhibiting the AV node, whereas drugs of thenifedipine family have a lesser inhibitory effect on the AV node. Nitricoxide (NO) indirectly promotes calcium channel closure. NO may be usedto inhibit contraction. NO may also be used to inhibit sympatheticoutflow, lessen the release of norepinephrine, cause vasodilation,decrease heart rate and decrease contractility. In the SA node,cholinergic stimulation leads to formation of NO.

[0129] Other drugs, drug formulations and/or drug compositions that maybe used according to this invention may include any naturally occurringor chemically synthesized sodium channel blocker. Sodium channelblockers are also known as sodium channel inhibitors, sodium channelblocking agents, rapid channel blockers or rapid channel inhibitors.Antiarrhythmic agents that inhibit or block the sodium channel are knownas class I antiarrhythmics, examples include, but are not limited to,quinidine and quinidine-like agents, lidocaine and lidocaine-likeagents, tetrodotoxin, encainide, flecainide and combinations, mixturesand/or salts thereof. Therefore, the term “sodium channel blocker”appearing herein may refer to one or more agents that inhibit or blockthe flow of sodium ions across a cell membrane or remove the potentialdifference across a cell membrane. For example, the sodium channel mayalso be totally inhibited by increasing the extracellular potassiumlevels to depolarizing hyperkalemic values, which remove the potentialdifference across the cell membrane. The result is inhibition of cardiaccontraction with cardiac arrest (cardioplegia). The opening of thesodium channel (influx of sodium) is for swift conduction of theelectrical impulse throughout the heart.

[0130] Other drugs, drug formulations and/or drug compositions that maybe used according to this invention may include any naturally occurringor chemically synthesized potassium channel agent. The term “potassiumchannel agent” appearing herein may refer to one or more agents thatimpact the flow of potassium ions across the cell membrane. There aretwo major types of potassium channels. The first type of channel isvoltage-gated and the second type is ligand-gated.Acetylcholine-activated potassium channels, which are ligand-gatedchannels, open in response to vagal stimulation and the release ofacetylcholine. Opening of the potassium channel causes hyperpolarizationwhich decreases the rate at which the activation threshold is reached.Adenosine is one example of a potassium channel opener. Adenosine slowsconduction through the AV node. Adenosine, a breakdown product ofadenosine triphosphate, inhibits the AV node and atria. In atrialtissue, adenosine causes the shortening of the action potential durationand causes hyperpolarization. In the AV node, adenosine has similareffects and also decreases the action potential amplitude and the rateof increase of the action potential. Adenosine is also a directvasodilator by its actions on the adenosine receptor on vascular smoothmuscle cells. In addition, adenosine acts as a negative neuromodulator,thereby inhibiting release of norepinephrine. Class III antiarrhythmicagents also known as potassium channel inhibitors lengthen the actionpotential duration and refractoriness by blocking the outward potassiumchannel to prolong the action potential. Amiodarone and d-sotalol areboth examples of class III antiarrhythmic agents.

[0131] Potassium is the most common component in cardioplegic solutions.High extracellular potassium levels reduce the membrane restingpotential. Opening of the sodium channel, which normally allows rapidsodium influx during the upstroke of the action potential, is thereforeinactivated because of a reduction in the membrane resting potential.The present invention may be combined with conventional CPB, the inducedasystole as described by this invention may serve as a substitute forconventional cardioplegic arrest. For example, the combination of drugsand vagal stimulation may be used as a cardioplegic agent in a varietyof medical procedures.

[0132] Drugs, drug formulations and/or drug compositions that may beused during according to this invention may comprise one or more of anynaturally occurring or chemically synthesized beta-blocker, cholinergicagent, cholinesterase inhibitor, calcium channel blocker, sodium channelblocker, potassium channel agent, adenosine, adenosine receptor agonist,adenosine deaminase inhibitor, dipyridamole, monoamine oxidaseinhibitor, digoxin, digitalis, lignocaine, bradykinin agents,serotoninergic agonist, antiarrythmic agents, cardiac glycosides, localanesthetics and combinations or mixtures thereof. Digitalis and digoxinboth inhibit the sodium pump. Digitalis is a natural inotrope derivedfrom plant material, while digoxin is a synthesized inotrope.Dipyridamole inhibits adenosine deaminase which breaks down adenosine.Drugs, drug formulations and/or drug compositions capable of reversiblysuppressing autonomous electrical conduction at the SA and/or AV node,while still allowing the heart to be electrically paced to maintaincardiac output may be used according to this invention.

[0133] In one embodiment, the cardiac asystole produced in accordancewith the present invention is reversible, e.g., chemically such as bythe administration of atropine or by natural forces. Beta-adrenergicstimulation or administration of calcium solutions may be used toreverse the effects of a calcium channel blocker such as verapamil.Agents that promote heart rate and/or contraction may be used in apreferred embodiment of the present invention. For example, dopamine, anatural catecholamine, is known to increase contractility. Positiveinotropes are agents that specifically increase the force of contractionof the heart. Glucagon, a naturally occurring hormone, is known toincrease heart rate and contractility. Glucagon may be used to reversethe effects of a beta-blocker since its effects bypass the betareceptor. Forskolin is known to increase heart rate and contractility.As mentioned earlier, epinephrine and norepinephrine naturally increaseheart rate and contractility. Thyroid hormone, phosphodiesteraseinhibitors and prostacyclin, a prostaglandin, are also known to increaseheart rate and contractility. In addition, methylxanthines are known toprevent adenosine from interacting with its cell receptors.

[0134] Typically, vagal nerve stimulation prevents the heart fromcontracting. This non-contraction must then be followed by periodswithout vagal nerve stimulation during which the heart is allowed tocontract, and blood flow is restored throughout the body.

[0135] At 517, sensor 6 may be checked to determine if an escape beat isimminent. The sensor may be checked periodically during the procedure,for example, as shown at 517. Alternatively, the sensor may interruptthe procedure at any point by indicating that an escape beat isimminent. For example, a visual and/or audible signal, such as aflashing light or beeping tone, may be used to alert a surgeon that anescape beat is imminent. If no contraction is imminent, then all or aportion of the medical procedure may be carried out (Block 520).However, if a contraction is imminent, then a signal may indicate anescape beat is about to occur (as seen at 523). If the sensor indicatesan escape beat is imminent, the surgeon may stop the medical procedureto allow the beat to occur. In one embodiment, the surgeon may thenproceed to Block 530, where the nerve stimulation is ceased and theheart is allowed to contract. Alternatively, unit 200 may automaticallyproceed to Block 530 to cease nerve stimulation when sensor 6 indicatesthat a beat is imminent.

[0136] The output of sensor 6 may be communicated to the surgeon by anumber of suitable means. For example, the output may be indicated on adisplay or monitor. A visual or audio signal may indicate when theelectrical signals from the heart reach a certain level, e.g. a levelindicating an imminent escape beat. Alternatively, the system of thepresent invention may “lock” the controls of the vagal stimulator in an“off” state when an escape beat is sensed. Alternatively, the system ofthe present invention may “lock” the controls of the surgicalinstruments being used to perform the surgery to indicate to the surgeonthat an escape beat is imminent. The system may then release thecontrols when the signals indicate that the heart is again appropriatelystilled.

[0137] Additionally, the amount of vagal nerve stimulation used and/orthe amount of drugs administered may be adjusted based on the output ofthe sensor 6. For example, the level of stimulation may be increased ifsensor 6 indicates that too many escape beats are occurring or arelikely to occur. This adjustment may be automatic or may be controlledby the surgeon.

[0138] At Block 520, a medical procedure may be performed or begun. Sucha procedure may be for example surgery on the heart. Alternatively, theprocedure may be surgery performed on another organ of the body. AtBlock 520, one or more of a variety of pharmacological agents or drugsmay be delivered or may continue to be delivered. These drugs mayproduce reversible asystole of a heart while maintaining the ability ofthe heart to be electrically paced. Other drugs may be administered fora variety of functions and purposes as described above.

[0139] The term “medical procedure” may mean any one or more medical orsurgical procedures such as, for example cardiac surgery, performed withor without cardiopulmonary bypass (CPB) circuits, heart valve repair,heart valve replacement, MAZE procedures, revascularization procedures,transmyocardial revascularization (TMR) procedures, percutaneousmyocardial revascularization (PMR) procedures, CABG procedures,anastomosis procedures, heart positioning procedures, non-surgicalprocedures, fluoroscopic procedures, beating heart surgery, vascularsurgery, neurosurgery, brain surgery, electrophysiology procedures,placement of one or more leads, diagnostic and therapeutic procedures,ablation procedures, ablation of arrhythmias, endovascular procedures,treatment of the liver, spleen, heart, lungs, and major blood vessels,aneurysm repair, imaging procedures of the heart and great vessels, CATscans or MRI procedures, pharmacological therapies, drug deliveryprocedures, gene therapies, cellular therapies, cancer therapies,radiation therapies, genetic, cellular, tissue and/or organ manipulationor transplantation procedures, coronary angioplasty procedures,placement or delivery of coated or noncoated stents, atherectomyprocedures, atherosclerotic plaque manipulation and/or removalprocedures, procedures where bleeding needs to be precisely controlled,procedures that require precise control of cardiac motion and/orbleeding.

[0140] When the medical procedure comprises one or more medical devices,e.g., coated stents, these devices may be coated with one or moreradioactive materials and/or biological agents such as, for example, ananticoagulant agent, an antithrombotic agent, a clotting agent, aplatelet agent, an anti-inflammatory agent, an antibody, an antigen, animmunoglobulin, a defense agent, an enzyme, a hormone, a growth factor,a neurotransmitter, a cytokine, a blood agent, a regulatory agent, atransport agent, a fibrous agent, a protein, a peptide, a proteoglycan,a toxin, an antibiotic agent, an antibacterial agent, an antimicrobialagent, a bacterial agent or component, hyaluronic acid, apolysaccharide, a carbohydrate, a fatty acid, a catalyst, a drug, avitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, anantiviral agent, a viral agent or component, a genetic agent, a ligandand a dye (which acts as a biological ligand). Biological agents may befound in nature (naturally occurring) or may be chemically synthesized.

[0141] The medical procedure may be non-invasive, minimally invasiveand/or invasive. The medical procedure may entail a port-accessapproach, a partially or totally endoscopic approach, a sternotomyapproach or a thoracotomy approach. The medical procedure may includethe use of various mechanical stabilization devices or techniques aswell as various robotic or imaging systems.

[0142] In one method, the heart may be temporarily slowed orintermittently stopped for short periods of time to permit the surgeonto accomplish the required surgical task and yet still allow the heartitself to supply blood circulation to the body. For example, stimulationof the vagus nerve in order to temporarily and intermittently slow orstop the heart is described in U.S. Pat. No. 6,006,134 entitled “Methodand Device for Electronically Controlling the Beating of a Heart UsingVenous Electrical Stimulation of Nerve Fibers,” Dec. 21, 1999, toinventors Hill and Junkman. This patent is assigned to Medtronic, Inc.and is incorporated herein by reference.

[0143] During the medical procedure, cardiac contractions or cardiacsignals may be monitored constantly or intermittently as describedabove. An assessment of the likelihood of a contraction may again betaken at Block 525. If no contraction is imminent, the physician maycontinue with the medical procedure that is in progress. However, if acontraction is likely to occur, the surgeon may increase nervestimulation and/or the administration of drugs. Alternatively, thesurgeon may choose to proceed to Block 530 and allow the heart to beatnormally for a period of time. The heart will therefore be allowed tocontract and thus blood will again be allowed to flow to the brain andvital organs.

[0144] After a time, the medical procedure or one phase of the procedureis completed at 520. After some phase of the medical procedure isperformed, cardiac contractions are allowed to occur (Block 530).Cardiac contractions may need to occur intermittently during theprocedure to ensure adequate blood flow. In one embodiment, thestimulation from the nerve stimulator 10 is stopped or slowed enough toallow the heart to contract. For example, the vagal nerve stimulation isremoved, thereby allowing cardiac contractions to occur.

[0145] In one embodiment of the present invention, it may be determinedif the heart is contracting as desired (532). If appropriate, the heartmay be stimulated to ensure that cardiac contractions occur (Block 535).For example, cardiac stimulator 20 may be used to apply pacing pulses tothe heart to encourage the heart to contract normally. In particular,the pacing pulses may be applied to the ventricle as is well known inthe field. Additionally, the amount of cardiac stimulation used may beadjusted based on the output of the sensor 6. For example, the level ofstimulation may be decreased or the duration of stimulation may bedecreased if the sensor 6 indicates that too many escape beats areoccurring or are likely to occur at such a level of stimulation.

[0146] The present invention permits the heart to be stilled orquiescent for selected and controllable periods of time in order topermit a medical procedure to be performed. While such a period ofquiescence is desired, it must not last too long, otherwise insufficientblood and oxygen is delivered to organs. Thus, it is necessary to havethe periods when the heart is beating (Blocks 530, 535). At Blocks 530,535, one or more of a variety of pharmacological agents or drugs may bedelivered or may continue to be delivered. These drugs may producereversible asystole of a heart while maintaining the ability of theheart to be electrically paced. Particularly at Blocks 530, 535, drugsmay be administered to encourage heart contractions. Other drugs may beadministered for a variety of functions and purposes as described above

[0147] Sensor 6 may also be used to determine whether the heart isbeating as desired at Block 532. Such output may be communicated to thesurgeon by a number of suitable means. For example, the output may beindicated on a display or monitor. A visual or audio signal may alsoindicate output. Alternatively, the system of the present invention may“lock” the controls of the cardiac stimulator in an “on” state after anescape beat has occurred in order to return the heart to a normal rate.Alternatively, the system of the present invention may “lock” thecontrols of the cardiac stimulator in an “off” state to prevent anescape beat. The system may then release the controls when theelectrical signals sensed by the sensor are again as desired.

[0148] At 539, it may be determined if additional medical procedures oradditional stages of medical procedures need to be performed. If so, theheart may again be stilled using the methods of stilling the heartdescribed above. The method may then be repeated (as in the loopdesignated by 540). For example, the heart may again be prevented fromcontracting by stimulation of the vagal nerve (510). Additional drugsmay be delivered or the drugs previously administered may continue to beadministered.

[0149] This cycle may be repeated until the procedure, such as surgery,is completed. As the cycle continues, sensor 6 enables monitoring ofheart rate and, if necessary, appropriate adjustment of nervestimulation and cardiac stimulation to ensure the heart is beatingappropriately.

[0150] For example, a surgical procedure at 520 may require severalstitches to be made by the surgeon. The surgeon may stimulate the vagalnerve at 510 to stop the heart. Then the surgeon may make the firststitch at 520. The surgeon may then reduce or halt stimulation at 530and allow the heart to contract. The surgeon may also pace the heart at535. Then at 540, the surgeon may return to 510 to inhibit contractionsof the heart. At 520, the surgeon will then make the second stitch. Thisprocess may be repeated (the loop designated by 540 may be repeated)until all the required stitches have been made. Meanwhile, the heart'selectrical signals are monitored continuously or, for example at Blocks517, 525 by sensor 6. The procedure may proceed uninterrupted if nocontractions are imminent.

[0151] After the procedure is completed, step 535 may be performed untilthe heart is beating normally. Once it has been determined at 539 thatthe medical procedure is complete, the surgeon may continue stimulatingthe heart until satisfied that the heart is beating normally.Additionally, sensor 6 may be used to monitor heart rate until it hasreached an acceptable level. At the procedure's end, one or more of avariety of pharmacological agents or drugs may be delivered or maycontinue to be delivered for example to alleviate pain or aid inrecuperation. Other drugs may be administered for a variety of functionsand purposes as described above.

[0152]FIG. 8 shows a flow diagram of one embodiment of the presentinvention. The patient is prepared for a medical procedure at 500. Oncethe patient is prepared, the initial state of cerebral blood circulationis measured (Block 505). Such measurements may include for example bloodflow, oxygen concentration, carbon dioxide concentration, etc. Theinitial state of cerebral blood circulation is then used as a gauge tocompare with the state of cerebral blood circulation during theprocedure.

[0153] At this point, a nerve that controls the beating of the heart isstimulated to slow down or stop the contractions of the heart (Block510). Such a nerve may be for example a vagal nerve. During this time,one or more of a variety of pharmacological agents or drugs, asdiscussed above, may be delivered to the patient (block 515). Thesedrugs may produce reversible asystole of a heart while maintaining theability of the heart to be electrically paced. Other drugs may beadministered for a variety of functions and purposes as described below.As seen in FIG. 8, drugs delivered at block 515 may be administered atthe beginning of the procedure, intermittently during the procedure,continuously during the procedure or following the procedure.

[0154] Typically, vagal nerve stimulation prevents the heart fromcontracting. This non-contraction must then be followed by periodswithout vagal nerve stimulation during which the heart is allowed tocontract, and blood flow is restored throughout the body. At block 517,the state of cerebral blood circulation may be monitored. Thismonitoring may occur at specific points during the procedure, forexample, as shown at block 517. Alternatively, monitoring may occurcontinuously. If cerebral blood circulation is sufficient, then all or aportion of the medical procedure may be carried out (Block 520).However, if the state of cerebral blood circulation is not sufficient,then a signal may indicate that the state of blood circulation to thebrain is insufficient. If the sensor indicates that the state of bloodcirculation is insufficient, the surgeon may proceed to block 530, wherethe nerve stimulation is ceased and the heart is allowed to contract.The cardiac stimulator may be used to cause the heart to contract.Alternatively, unit 200 may automatically proceed to block 530 to ceasenerve stimulation. In addition, Unit 200 may automatically begin cardiacstimulation.

[0155] The state of cerebral blood circulation sensed by sensor 6 may becommunicated to the surgeon by a number of suitable means. For example,the ambient blood flow may be indicated on a display or monitor. Avisual or audio signal may indicate when the level of cerebral bloodflow reaches a certain level, e.g. when blood flow is insufficient.Alternatively, the system of the present invention may “lock” thecontrols of the vagal stimulator in an “off” state when cerebral bloodflow reaches a predetermined condition, thereby indicating that bloodflow is insufficient. The system may then release the controls when thestate of cerebral blood circulation sensed by the sensor is againsufficient.

[0156] Additionally, the amount of vagal nerve stimulation used may beadjusted based on the output of the sensor 6. For example, the level ofstimulation may be lowered or the duration of stimulation may be loweredif the sensor indicates that cerebral blood circulation at 517 isinsufficient. This adjustment may be automatic or may be controlled bythe surgeon. At block 520, a medical procedure, as described above, maybe performed or begun.

[0157] During the medical procedure, the state of cerebral bloodcirculation may be monitored constantly or intermittently as describedabove. An assessment, for example, of the amount of blood flowing to thebrain may again be taken at block 525. If the state of cerebral bloodcirculation is sufficient, the physician may continue with the medicalprocedure that is in progress. However, if the state of cerebral bloodcirculation is not sufficient, then sensor 6 may indicate that bloodcirculation to the brain is insufficient. If the sensor indicates thatblood circulation is insufficient, the surgeon may proceed to block 530,where the nerve stimulation is ceased. The heart will therefore beallowed to contract and thus blood will again be allowed to flow to thebrain and vital organs. The cardiac stimulator may be used to cause theheart to contract. Alternatively, unit 200 may automatically proceed toblock 530 to cease nerve stimulation. In addition, Unit 200 mayautomatically begin cardiac stimulation. Additionally, the amount ofvagal nerve stimulation used may be adjusted based on the output of thesensor 6. For example, the level of stimulation may be lowered or theduration of stimulation may be lowered if the sensor indicates thatcerebral blood circulation at 525 is insufficient.

[0158] After a time, the medical procedure or one phase of the procedureis completed at 520. After some phase of the medical procedure isperformed, cardiac contractions are allowed to occur (block 530).Cardiac contractions may need to occur intermittently during theprocedure to ensure adequate blood flow. In one embodiment, thestimulation from the nerve stimulator 10 is stopped or slowed enough toallow the heart to contract. For example, the vagal nerve stimulation isremoved, thereby allowing cardiac contractions to occur.

[0159] In another embodiment, the heart may be stimulated to ensure thatcardiac contractions occur (block 535). For example, cardiac stimulator20 may be used to apply pacing pulses to the heart to encourage theheart to contract normally. In particular, the pacing pulses may beapplied to the ventricle as is well known in the field. Additionally,the amount of cardiac stimulation used may be adjusted based on theoutput of the sensor 6. For example, the level of stimulation may beincreased or the duration of stimulation may be increased if the sensorindicates that cerebral blood circulation at 525 is insufficient.

[0160] The present invention permits the heart to be stilled orquiescent for selected and controllable periods of time in order topermit a medical procedure to be performed. While such a period ofstillness or quiescence is desired, it must not last too long, otherwiseinsufficient blood and oxygen is delivered to organs. Thus, it isnecessary to have the periods when the heart is beating (blocks 530,535).

[0161] The state of cerebral blood circulation, for example, sensed bysensor 6 while the heart is beating may be communicated to the surgeonby a number of suitable means. For example, ambient blood flow may beindicated on a display or monitor. A visual or audio signal may indicatewhen the level of cerebral blood flow reaches a certain level, e.g. whenblood flow is insufficient. Alternatively, the system of the presentinvention may “lock” the controls of the cardiac stimulator in an “on”state when the state of cerebral blood circulation reaches apredetermined condition, thereby indicating that blood circulation isinsufficient. The system may then release the controls when the state ofblood circulation sensed by the sensor is again sufficient.

[0162] If additional medical procedures or additional stages of medicalprocedures need to be performed, the heart may again be stilled usingthe methods of stilling the heart described above. Therefore from block530 or block 535, the method may be repeated (as in the loop designatedby 540). For example, the heart may again be prevented from contractingby stimulation of the vagal nerve (510). Additional drugs may bedelivered or the drugs previously administered may continue to beadministered.

[0163] This cycle may be repeated until the procedure, such as thesurgery, is completed. As the cycle continues, sensor 6 enablesmonitoring of the state of blood circulation and, if necessary,appropriate adjustment of nerve stimulation and cardiac stimulation toensure sufficient blood circulation.

[0164] For example, the surgical procedure at 520 may require severalstitches to be made by the surgeon. The surgeon may stimulate the vagalnerve at 510 to stop the heart. Then the surgeon may make the firststitch at 520. The surgeon may then reduce or halt stimulation at 530and allow the heart to contract. The surgeon may also pace the heart at535. Then at 540, the surgeon may return to 510 to inhibit contractionsof the heart. At 520, the surgeon will then make the second stitch. Thisprocess may be repeated (the loop designated by 540 may be repeated)until all the required stitches have been made. Meanwhile, the state ofblood circulation is monitored continuously or, for example at blocks517 and 525 by sensor 6. The procedure may proceed uninterrupted if thestate of blood circulation remains sufficient.

[0165] If required, after the procedure is completed, step 535 may beperformed until the heart is beating normally. Step 545 may be continueduntil the physician is satisfied that the heart is beating normally andthe state of blood circulation has reached an acceptable level.

[0166]FIG. 9 is a timeline showing the relation of the vagal nervestimulation to the cardiac stimulation in one embodiment of the presentinvention.

[0167] Point 610 indicates a point before the medical procedure hasbegun. At this point 610, both nerve stimulation and cardiac stimulationare off. At point 610, the heart is beating regularly. Then nervestimulation is turned on to inhibit beating of the heart. During phase601, the vagal nerve stimulation is on and the cardiac stimulation isoff. This is the condition of the two types of stimulation at step 520described above. Point 611 is a representative point during phase 601.At point 611, the contractions of the heart are stilled or substantiallyslowed. Then during phase 602 the vagal stimulation is turned off (asdescribed at step 530) and the cardiac stimulation may be turned on (asdescribed at 535). Point 612 is a representative point during phase 602.At point 612, the contractions are allowed and/or may be induced. Duringphase 603, the vagal nerve stimulation is again turned on and thecardiac stimulation is turned off. Then during phase 604 the vagalstimulation is again turned off and the cardiac stimulation may again beturned on. The method of the present invention may be repeated asnecessary until a point is reached, represented by point 615, when thenecessary medical procedures are completed. At this point 615, nervestimulation is off although cardiac stimulation may be left on in orderto pace the heart to its normal rhythm.

[0168]FIG. 10 is a timeline illustrating a relationship between asensor, a nerve stimulator and a cardiac stimulator in one embodiment ofthe present invention. Point 610 indicates a point before the medicalprocedure has begun. At this point 610, both nerve stimulation andcardiac stimulation are off. At point 610, the heart is beatingregularly. The patient's heart rate may be measured by sensor 6 at point610. Thus, sensor 6 may be turned on at point 610.

[0169] Then nerve stimulation is turned on to inhibit beating of theheart. During phase 601, the vagal nerve stimulation is on and thecardiac stimulation is off. This is the condition of the two types ofstimulation at step 520 described above. In one embodiment, as shown inFIG. 10, sensor 6 is on throughout the entire procedure. Alternatively,sensor 6 may be turned on during phase 601 to check, for example,whether a contraction is imminent or the state of cerebral bloodcirculation is adequate (Block 517).

[0170] Point 611 is a representative point during phase 601. At point611, the contractions of the heart are stilled or substantially slowed.In addition, at point 611, sensor 6 may be used, for example, todetermine that no contractions are imminent or if cerebral bloodcirculation is adequate (as described at Blocks 517 and 525). If nocontractions are impending or if cerebral blood circulation is adequateat point 611, then the medical procedure can proceed (as described atBlock 520). However, if a contraction is impending or cerebral bloodcirculation is not adequate at point 611, sensor 6 may provide a signalindicating the impending contraction or inadequate cerebral bloodcirculation. The surgeon may then stop the medical procedure and allowthe heart to beat. After one or more cardiac contractions have occurred,the surgeon may then continue in phase 601 and finish the step of theprocedure. Alternatively, the surgeon may proceed immediately to phase602 after one or more contractions have occurred. Alternatively, controlunit 200 may automatically proceed to phase 602 after providing thesignal.

[0171] During phase 602 the vagal stimulation is turned off (asdescribed at step 530) and the cardiac stimulation may be turned on (asdescribed at 535). Point 612 is a representative point during phase 602.At point 612, the contractions are allowed and/or may be induced. In oneembodiment, sensor 6 is still on during phase 602 and may be used todetermine if the contractions are occurring appropriately or if bloodcirculation is occurring appropriately. Alternatively, the sensor 6 maybe turned on during phase 602 to determine if the contractions areoccurring appropriately.

[0172] During phase 603, the vagal nerve stimulation is again turned onand the cardiac stimulation is turned off. In one embodiment, sensor 6has been operating throughout each phase and continues to operatethrough phase 603. The amount or duration of vagal stimulation duringphase 603 may be different than the amount or duration of vagalstimulation during phase 601, based on the data gathered from sensor 6during phase 601. For example, the vagal stimulation may be increased ifsensor 6 detected an undesirable number of escape beats. Alternatively,sensor 6 may be turned on during phase 603 to again determine if anescape beat is imminent (as described at Block 525) or if cerebral bloodcirculation in adequate. Point 613 is a representative point duringphase 603. If no escape beat is imminent at 613 or if cerebral bloodcirculation is adequate, then the medical procedure can proceed (asdescribed in step 520). However, if an escape beat is impending of ifcerebral blood circulation is inadequate, sensor 6 may provide a signalindicating this. The surgeon may then stop the medical procedure andallow the heart to beat. After the heart has beated, the surgeon maythen continue in phase 603 and finish the step of the procedure.Alternatively, the surgeon may proceed immediately to phase 604 afterone or more contractions have occurred. Alternatively, control unit 200may automatically proceed to phase 604 after providing the signal.

[0173] During phase 604 the vagal stimulation is again turned off andthe cardiac stimulation may again be turned on. The amount or durationof cardiac stimulation during phase 604 may be different than the amountor duration of cardiac stimulation during phase 602, based on the datagathered from sensor 6 during the previous phases. For example, theamount or duration of cardiac stimulation may be decreased if too manyescape beats occurred during the previous phases. Point 614 is arepresentative point during phase 602. At point 614, the contractionsare allowed and/or may be induced. In one embodiment, sensor 6 is stillon during phase 604 and may be used to determine if the contractions areoccurring appropriately or if cerebral blood circulation is occurringadequately. Alternatively, sensor 6 may be turned on during phase 604 todetermine if the contractions are occurring appropriately.

[0174] The method of the present invention may be repeated as necessaryuntil a point is reached, represented by point 615, when the necessarymedical procedures are completed. At this point 615, nerve stimulationis off although cardiac stimulation may be left on in order to pace theheart to its normal rhythm. At point 615, sensor 6 may be used to checkthe heart rate or cerebral blood circulation for a final time (asdescribed at 532).

[0175]FIG. 11 shows a schematic view of one embodiment of a system ofthe present invention for performing a medical procedure in accordancewith the present invention at 100. System 100 comprises a vasoactivedrug delivery system 7, a nerve stimulator 10, and a cardiac stimulator20. System 100 may include controller 30 and breathing regulator 40.

[0176] Drug delivery system 7 preferably includes a vasodilativedelivery component 17 and a vasoconstrictive delivery component 27. Bothdelivery components 17, 27 may be any suitable means for deliveringdrugs to a site of a medical procedure. For example drug delivery system7 may be a system for delivering a vasodilative spray 17 and avasoconstrictive spray 27. Drug delivery system 7 may be a system fordelivering a vasodilative cream and a vasoconstrictive cream. Drugdelivery system 7 may also be a system for delivering any vasodilativeformulation 17 such as an ointment or medicament etc. and anyvasoconstrictive formulation 27 such as an ointment or medicament etc.or any combination thereof.

[0177] Drug delivery system 7 may comprise a catheter, such as a drugdelivery catheter or a guide catheter, for delivering a vasodilativesubstance 17 followed by a vasoconstrictive substance 27. A drugdelivery catheter may include an expandable member, e.g., a low-pressureballoon, and a shaft having a distal portion, wherein the expandablemember is disposed along the distal portion. A catheter for drugdelivery may comprise one or more lumens and may be deliveredendovascularly via insertion into a blood vessel, e.g., an artery suchas a femoral, radial, subclavian or coronary artery. The catheter can beguided into a desired position using various guidance techniques, e.g.,flouroscopic guidance and/or a guiding catheter or guide wiretechniques. In one embodiment, one catheter is used to deliver both thevasodilative component and the vasoconstrictive component. Drug deliverysystem 7 may also be a patch, such as a transepicardial patch thatslowly releases drugs directly into the myocardium, a cannula, a pumpand/or a hypodermic needle and syringe assembly.

[0178] Drug delivery system 7 may also be an iontophoretic drug deliverydevice placed on the heart. In general, the delivery of ionized drugsmay be enhanced via a small current applied across two electrodes.Positive ions may be introduced into the tissues from the positive pole,or negative ions from the negative pole. The use of iontophoresis maymarkedly facilitate the transport of certain ionized drug molecules. Forexample, lidocaine hydrochloride may be applied to the heart via a drugpatch comprising the drug. A positive electrode could be placed over thepatch and current passed. The negative electrode would contact the heartor other body part at some desired distance point to complete thecircuit.

[0179] Drug delivery system 7 may be any suitable system for deliveringa vasodilative component followed by a vasoconstrictive component or fordelivering any appropriate vasoactive formulation.

[0180] A vasodilative component 17 may comprise one or more vasodilativedrugs in any suitable formulation or combination. Examples ofvasodilative drugs include, but are not limited to, a vasodilator, anorganic nitrate, isosorbide mononitrate, a mononitrate, isosorbidedinitrate, a dinitrate, nitroglycerin, a trinitrate, minoxidil, sodiumnitroprusside, hydralazine hydrochloride, nitric oxide, nicardipinehydrochloride, fenoldopam mesylate, diazoxide, enalaprilat, epoprostenolsodium, a prostaglandin, milrinone lactate, a bipyridine and a dopamineD1-like receptor agonist, stimulant or activator. The vasodilativecomponent 17 may include a pharmaceutically acceptable carrier orsolution in an appropriate dosage. Pharmaceutically acceptable carriersinclude a number of solutions, preferably sterile, for example, water,saline, Ringer's solution and/or sugar solutions such as dextrose inwater or saline. Other possible carriers that may be used include sodiumcitrate, citric acid, amino acids, lactate, mannitol, maltose, glycerol,sucrose, ammonium chloride, sodium chloride, potassium chloride, calciumchloride, sodium lactate, and/or sodium bicarbonate. Carrier solutionsmay or may not be buffered. The vasodilative component 17 may includeantioxidants or preservatives such as ascorbic acid. They may also be ina pharmaceutically acceptable form for parenteral administration, forexample to the cardiovascular system, or directly to the heart, such asintracoronary infusion or injection. Drug formulations or compositionsmay comprise agents that provide a synergistic effect when administeredtogether. A synergistic effect between two or more drugs or agents mayreduce the amount that normally is required for therapeutic delivery ofan individual drug or agent. Two or more drugs may be administered, forexample, sequentially or simultaneously. Drugs may be administered viaone or more bolus injections and/or infusions or combinations thereof.The injections and/or infusions may be continuous or intermittent.

[0181] The vasoconstrictive component 27 may comprise one or moresuitable vasoconstrictive drugs in any suitable formulation orcombination. Examples of vasoconstrictive drugs include, but are notlimited to, a vasoconstrictor, a sympathomimetic, methoxaminehydrochloride, epinephrine, midodrine hydrochloride, desglymidodrine,and an alpha-receptor agonist, stimulant or activator. Thevasoconstrictive component 27 may include a pharmaceutically acceptablecarrier or solution in an appropriate dosage. Pharmaceuticallyacceptable carriers include a number of solutions, preferably sterile,for example, water, saline, Ringer's solution and/or sugar solutionssuch as dextrose in water or saline. Other possible carriers that may beused include sodium citrate, citric acid, amino acids, lactate,mannitol, maltose, glycerol, sucrose, ammonium chloride, sodiumchloride, potassium chloride, calcium chloride, sodium lactate, and/orsodium bicarbonate. Carrier solutions may or may not be buffered. Thevasoconstrictive component 27 may include antioxidants or preservativessuch as ascorbic acid. They may also be in a pharmaceutically acceptableform for parenteral administration, for example to the cardiovascularsystem, or directly to the heart, such as intracoronary infusion orinjection. Drug formulations or compositions may comprise agents thatprovide a synergistic effect when administered together. A synergisticeffect between two or more drugs or agents may reduce the amount thatnormally is required for therapeutic delivery of an individual drug oragent. Two or more drugs may be administered, for example, sequentiallyor simultaneously. Drugs may be administered via one or more bolusinjections and/or infusions or combinations thereof. The injectionsand/or infusions may be continuous or intermittent.

[0182] All or a portion of drug delivery system 7 may be placed in anysuitable manner for application of drugs to the heart. In oneembodiment, system 7 is placed to deliver drugs directly to a vessel ofthe heart. Drug delivery system 7 may be placed invasively ornon-invasively. In one embodiment, all or a portion of drug deliverysystem 7 is implanted adjacent the target area of the heart.Alternatively, all or a portion of drug delivery system 7 is removablyapplied to the target area of the heart. For example, system 7 maycomprise a vasodilative cream manually applied to the target sitefollowed by a vasoconstrictive spray manually applied to the site.Alternatively, system 7 may comprise a guidable or steerable mechanism,such as a catheter, which allows its position to be adjusted during themedical procedure. System 7 may be positioned endoscopically and othersuitable placements of system 7, such as on or near a target coronaryartery and/or vein, a pulmonary artery and/or vein, the right atriumand/or ventricle, the left atrium and/or ventricle, the aorta, the AVnode, and/or the coronary sinus. System 7 may also be positioned toadminister or deliver drugs via intravenous, intracoronary and/orintraventricular administration in a suitable carrier. Examples ofarteries that may be used to deliver drugs to the AV node include the AVnode artery, the right coronary artery, the right descending coronaryartery, the left coronary artery, the left anterior descending coronaryartery and Kugel's artery.

[0183] All or a portion of drug delivery system 7 may also be placed inany suitable manner for application of drugs to another area of the bodysuch as the leg or another limb. For example, the system 7 may be placedto apply vasoactive substances to a saphenous vein to be harvested or toany other suitable graft vessel. In one embodiment, system 7 is placedto deliver drugs directly to a suitable graft vessel. Drug deliverysystem 7 may be placed invasively or non-invasively. In one embodiment,drug delivery system 7 is implanted adjacent the graft vessel.Alternatively, drug delivery system is removably applied to the graftvessel.

[0184] Drug delivery system 7 may be powered by AC current, DC currentor it may be battery powered by a disposable or re-chargeable battery.Drug delivery system 7 may comprise a surgeon controlled switch box. Aswitch, or all of drug delivery system 7 may also be incorporated in oron one of the surgeon's instruments, such as surgical site retractor, orany other location easily and quickly accessed by the surgeon fordelivery of drugs by the surgeon. The switch may be, for example, a handswitch, a foot switch, or a voice-activated switch comprisingvoice-recognition technologies.

[0185] A visual and/or audible signal used to alert a surgeon to thecompletion or resumption of vasodilative or vasoconstrictive drugs maybe incorporated into system 7. For example, a beeping tone or flashinglight may be used to indicate that a vasodilative drug is beingdelivered followed by a different tone or light to indicate that avasoconstrictive drug is being delivered.

[0186] Drug delivery system 7 may be slaved to nerve stimulator 10 orcardiac stimulator 20. Software controlling drug delivery system may bedesigned to automatically deliver drugs while nerve stimulator 10 orcardiac stimulator 20 is on.

[0187] Drug delivery system 7, nerve stimulator 10 and/or cardiacstimulator 20 may be slaved to a robotic system or a robotic system maybe slaved to drug delivery system 7, nerve stimulator 10 and/or cardiacstimulator 20. Breathing regulator 40 and other components, as describedabove, may also be slaved to such a system.

[0188]FIG. 12 shows one embodiment of the present invention at 200. Inthis embodiment, the elements named above may be combined or connectedto a control unit along with other components. The unit 200 may be usedto coordinate the various elements. Unit 200 may incorporate acontroller or any suitable processor 230.

[0189] Drug delivery system 207 may be incorporated into unit 200. Forexample, FIG. 12 shows drug delivery system 207, including avasodilative needle assembly 217 for delivery of vasodilative drugs anda vasoconstrictive needle assembly 227 for delivery of vasoconstrictivedrugs. Different positions of the vasodilative component 217 andvasoactive component 227 are accessible through various access openings,for example, in the cervical or thorax regions. Drug delivery system 207or components of drug delivery system may be positioned through athoracotomy, sternotomy, endoscopically through a percutaneous port,through a stab wound or puncture, through a small incision in the neckor chest, through the internal jugular vein, the esophagus, the trachea,placed on the skin or in combinations thereof.

[0190] Drug delivery system 207 may be in communication with a processor230 as shown in FIG. 12. The processor may thus be used to process theadministration of drugs delivered by system 207. The processor may storeinformation about the drugs being delivered such as dosage amounts andwhen particular dosages have been delivered.

[0191] Controller 230 may be used to gather information from drugdelivery system 207, nerve stimulation electrodes 210 and cardiacstimulation electrodes 220. Controller 230 may also be used to controlthe stimulation levels and stimulation duration of nerve stimulationelectrodes 210 and cardiac stimulation electrodes 220 or the drugdelivery levels and duration of system 207. Controller 230 may alsogather and process information from the various components of system100. This information may be used to adjust stimulation levels andstimulation times of nerve stimulation electrodes 210 and cardiacstimulation electrodes 220 or the drug delivery levels and duration ofsystem 207.

[0192] As described above, unit 200 may incorporate one or more switchesto facilitate regulation of the various components by the surgeon. Onceexample of such a switch is shown as foot pedal 250. The switch may alsobe, for example, a hand switch, or a voice-activated switch comprisingvoice-recognition technologies. The switch may be incorporated in or onone of the surgeon's instruments, such as surgical site retractor, orany other location easily and quickly accessed by the surgeon. Unit 200may also include a display 260. Unit 200 may also include other means ofindicating the status of various components to the surgeon such as anumerical display, gauges, a monitor display or audio feedback. Unit 200may also include one or more visual and/or audible signals used toprepare a surgeon for the start or stop of nerve stimulation and/orcardiac stimulation.

[0193]FIG. 13 shows a flow diagram of one embodiment of the presentinvention. The patient is prepared for a medical procedure at 500.

[0194] At block 510, a nerve that controls the beating of the heart isstimulated. Such a nerve may be for example a vagal nerve. During thistime, one or more of a variety of pharmacological agents or drugs, asdescribed above, may be delivered locally or systemically in addition tothe locally administered vasoactive drugs delivered by system 7 (block517). These drugs may produce reversible asystole of a heart whilemaintaining the ability of the heart to be electrically paced. In oneembodiment of the invention, a vasodilator is delivered at block 517.Other drugs may be administered for a variety of functions and purposesas described below. Drugs delivered in addition to the vasoactive drugsmay be administered at the beginning of the procedure, intermittentlyduring the procedure, continuously during the procedure or following theprocedure.

[0195] At block 517, a vasoactive drug is delivered to the site of themedical procedure. In one embodiment, a vasodilative drug is deliveredlocally using vasodilative delivery component 17. The drug may beapplied directly to a vessel in order to cause the vessel to dilate.Such a dilated vessel is easier to view and provides an enlarged fieldupon which to perform the procedure.

[0196] At block 520, a medical procedure, as described above, may beperformed or begun. Such a procedure may be, for example, surgery on theheart. In one embodiment, the procedure may be surgery on the vesselupon which the vasodilative formulation has been delivered.Alternatively, the procedure may be surgery performed on another organor another vessel in another organ of the body. For example, a graftvessel, such as the saphenous vein, may be harvested at this point.

[0197] As seen in FIG. 13, an additional vasoactive drug or drugformulation may be delivered to the site of the medical procedure atblock 527 in one embodiment of the invention. For example, avasoconstrictive drug may be delivered locally using vasoconstrictivedelivery component 17. The drug may be applied directly to a vessel inorder to cause the vessel to constrict, particularly to constrict to itsusual size. Such a constricted vessel may now perform its usualfunctions.

[0198] After a time, the medical procedure or one phase of the procedureis completed. After some phase of the medical procedure is performed,cardiac contractions are allowed to occur (block 530). Cardiaccontractions may need to occur intermittently during the procedure toensure adequate blood flow. In one embodiment, the stimulation from thenerve stimulator 10 is stopped or slowed enough to allow the heart tocontract. For example, the vagal nerve stimulation is removed, therebyallowing cardiac contractions to occur.

[0199] In another embodiment, the heart may be stimulated to ensure thatcardiac contractions occur (block 535). For example, cardiac stimulator20 may be used to apply pacing pulses to the heart to encourage theheart to contract normally. In particular, the pacing pulses may beapplied to the ventricle as is well known in the field.

[0200] The present invention permits the heart to be stilled forselected and controllable periods of time in order to permit a medicalprocedure to be performed. While such a period of stillness is desired,it must not last too long, otherwise insufficient blood and oxygen isdelivered to organs. Thus, it is necessary to have the periods when theheart is beating (blocks 530, 535).

[0201] If additional medical procedures or additional stages of medicalprocedures need to be performed, the heart may again be stilled usingthe methods of stilling the heart described above. Therefore, from block530 or block 535, the method may be repeated (block 540). For example,the heart may again be prevented from contracting by stimulation of thevagal nerve (510). Additional delivery of a vasodilative formulation(block 517) followed by, for example, surgery (block 520) followed bydelivery of a vasoconstrictive formulation (block 527) may occur on thesame or a different vessel. Additional drugs may be delivered or thedrugs previously administered may continue to be administered.

[0202] Additional steps of the medical procedure or additional medicalprocedures may be performed (Block 520) while the heart is still. Thenthis stage of stillness may be followed by another stage when thestimulation is removed (block 530) and the heart is allowed to contract.Again, the heart may be stimulated to encourage contractions (block535).

[0203] This cycle may be repeated until the procedure, such as surgery,is completed. After the procedure is completed, step 535 may beperformed until the heart is beating normally.

[0204] For example, a surgical procedure at 520 may require severalstitches to be made by the surgeon. The surgeon may stimulate the vagalnerve at 510 to stop the heart. The surgeon may then apply thevasodilative formulation at 517 to facilitate viewing of andmanipulation of the vessel to be stitched. Then the surgeon may make thefirst stitch at 520. The surgeon may apply a vasoconstrictiveformulation if appropriate at 527. The surgeon may then reduce or haltstimulation at 530 and allow the heart to contract. The surgeon may alsopace the heart at 535. Then at 540, the surgeon may return to 510 toinhibit contractions of the heart. At 520, the surgeon will then makethe second stitch. This process may be repeated (the loop designated by540 may be repeated) until all the required stitches have been made.Alternatively, the surgeon may apply the vasocontrictive formulation atblock 545 after all the required stitches have been made.

[0205] In one embodiment, after the surgery is completed, step 535 isperformed until the heart is beating normally. At the procedure's end,one or more of a variety of pharmacological agents or drugs may bedelivered or may continue to be delivered for example to alleviate painor aid in recuperation. Other drugs may be administered for a variety offunctions and purposes as described above.

[0206]FIG. 14 is a timeline illustrating one embodiment of therelationship between vasoactive drug delivery, vagal nerve stimulationand cardiac stimulation.

[0207] Point 610 indicates a point before the medical procedure hasbegun. At this point 610, both nerve stimulation and cardiac stimulationare off. At point 610, the heart is beating regularly. Then nervestimulation is turned on to inhibit beating of the heart. During phase601, the vagal nerve stimulation is on and the cardiac stimulation isoff. This is the condition of the two types of stimulation at step 520described above.

[0208] Point 611 is a representative point during phase 601. At point611, the contractions of the heart are stilled or substantially slowed.A vasoactive formulation may be delivered at point 612, once the heartis still or substantially slowed. After all or a portion of the medicalprocedure is performed during phase 601, a vasoconstrictive substancemay be delivered at point 613, which is a point near the end of phase601. Alternatively, the vasoconstrictive substance may be applied at alater time.

[0209] During phase 602 the vagal stimulation is turned off (asdescribed at step 530) and the cardiac stimulation may be turned on (asdescribed at 535). Point 614 is a representative point during phase 602.At point 614, the contractions are allowed and/or may be induced.

[0210] During phase 603, the vagal nerve stimulation is again turned onand the cardiac stimulation is turned off. Vasoactive substances mayagain be delivered during phase 603 in an appropriate manner. Theamounts or types of vasoactive substances delivered during phase 603 maybe the same or different from those delivered during phase 601. In oneembodiment, phase 603 is the final phase of the medical procedure and atpoint 615, which is a point after the medical procedure has beencompleted, a vasoconstrictive formulation may be delivered.

[0211] Alternatively, the procedure may enter a phase represented byphase 604. During phase 604 the vagal stimulation is again turned offand the cardiac stimulation may again be turned on. Point 616 is arepresentative point during phase 604. At point 616, the contractionsare allowed and/or may be induced.

[0212] The method of the present invention may be repeated as necessaryuntil a point is reached, represented by point 617, when the necessarymedical procedures are completed. At this point 617, nerve stimulationis off although cardiac stimulation may be left on in order to pace theheart to its normal rhythm. Vasoconstrictive drugs or other drugs may bedelivered at point 617.

[0213] It will be appreciated by those skilled in the art that while theinvention has been described above in connection with particularembodiments and examples, the invention is not necessarily so limited,and that numerous other embodiments, examples, uses, modifications anddepartures from the embodiments, examples and uses are intended to beencompassed by the claims attached hereto. The entire disclosure of eachpatent and publication cited herein is incorporated by reference, as ifeach such patent or publication were individually incorporated byreference herein.

We claim:
 1. A method of performing a medical procedure, comprising:providing a first electrode for supplying electrical current;positioning the first electrode adjacent a vagal nerve; providing asecond electrode for supplying electrical current; positioning thesecond electrode adjacent a phrenic nerve; supplying electrical currentto the first electrode to stimulate the vagal nerve to control heartrate; and supplying electrical current to the second electrode tostimulate the phrenic nerve to control breathing, wherein the supplyingof electrical current to the first and second electrodes is coordinated.2. The method of claim 1, wherein the first electrode is positionedthrough a thoracotomy.
 3. The method of claim 1, wherein the firstelectrode is positioned through a sternotomy.
 4. The method of claim 1,wherein the first electrode is positioned through a percutaneous port.5. The method of claim 1, wherein the first electrode is positionedthrough a small incision.
 6. The method of claim 1, wherein the secondelectrode is positioned through a thoracotomy.
 7. The method of claim 1,wherein the second electrode is positioned through a sternotomy.
 8. Themethod of claim 1, wherein the second electrode is positioned through apercutaneous port.
 9. The method of claim 1, wherein the secondelectrode is positioned through a small incision.
 10. The method ofclaim 1, wherein the first electrode is positioned in a trachea.
 11. Themethod of claim 1, wherein the first electrode is positioned in anesophagus.
 12. The method of claim 1, wherein the first electrode ispositioned in a blood vessel.
 13. The method of claim 12, wherein theblood vessel is an internal jugular vein.
 14. The method of claim 1,wherein the second electrode is positioned in a blood vessel.
 15. Themethod of claim 14, wherein the blood vessel is an internal jugularvein.
 16. The method of claim 1 further comprising: administering atleast one drug during the medical procedure.
 17. A method of performinga medical procedure, comprising: providing a first electrode forsupplying electrical current; positioning the first electrode adjacent aheart; providing a second electrode for supplying electrical current;positioning the second electrode adjacent a phrenic nerve; supplyingelectrical current to the first electrode to stimulate the heart tocontract; and supplying electrical current to the second electrode tostimulate the phrenic nerve to control breathing, wherein the supplyingof electrical current to the first and second electrodes is coordinated.18. The method of claim 1, wherein the first electrode is positionedthrough a thoracotomy.
 19. The method of claim 1, wherein the firstelectrode is positioned through a sternotomy.
 20. The method of claim 1,wherein the first electrode is positioned through a percutaneous port.21. The method of claim 1, wherein the first electrode is positionedthrough a small incision.
 22. The method of claim 1, wherein the secondelectrode is positioned through a thoracotomy.
 23. The method of claim1, wherein the second electrode is positioned through a sternotomy. 24.The method of claim 1, wherein the second electrode is positionedthrough a percutaneous port.
 25. The method of claim 1, wherein thesecond electrode is positioned through a small incision.
 26. The methodof claim 1, wherein the first electrode is positioned in a trachea. 27.The method of claim 1, wherein the first electrode is positioned in anesophagus.
 28. The method of claim 1, wherein the first electrode ispositioned in a blood vessel.
 29. The method of claim 1, wherein thesecond electrode is positioned in a blood vessel.
 30. The method ofclaim 24, wherein the blood vessel is an internal jugular vein.
 31. Themethod of claim 1 further comprising: administering at least one drugduring the medical procedure.
 32. A system for performing a medicalprocedure, comprising: a nerve stimulator to inhibit beating of theheart; a phrenic nerve stimulator to control breathing; and means forcoordinated regulation of the output of the phrenic nerve stimulator andthe output of the nerve stimulator to inhibit beating of the heart. 33.The system of claim 32 further comprising: drug delivery means fordelivering at least one drug during the medical procedure.
 34. Thesystem of claim 33 wherein the drug delivery means is selected from thegroup consisting of: a spray, a cream, an ointment, a medicament, apill, a patch, a catheter, a cannula, a needle and syringe, a pump, andan iontophoretic drug delivery device.
 35. The system of claim 32wherein the nerve stimulator to inhibit beating of the heart comprisesat least one electrode.
 36. The system of claim 35 wherein the electrodeis selected from the group consisting of: nerve stimulation electrodes,endotracheal electrodes, endoesophageal electrodes, intravascularelectrodes, transcutaneous electrodes, intracutaneous electrodes,balloon-type electrodes, basket-type electrodes, umbrella-typeelectrodes, tape-type electrodes, suction-type electrodes, screw-typeelectrodes, barb-type electrodes, bipolar electrodes, monopolarelectrodes, metal electrodes, wire electrodes, patch electrodes, cuffelectrodes, clip electrodes, needle electrodes and probe electrodes. 37.The system of claim 32 wherein the phrenic nerve stimulator comprises atleast one electrode.
 38. The system of claim 37 wherein the electrode isselected from the group consisting of: intravascular electrodes,patch-type electrodes, balloon-type electrodes, basket-type electrodes,umbrella-type electrodes, tape-type electrodes, cuff-type electrodes,suction-type electrodes, screw-type electrodes, barb-type electrodes,bipolar electrodes, monopolar electrodes, metal electrodes, wireelectrodes, endotrachael electrodes, endoesophageal electrodes,transcutaneous electrodes, intracutaneous electrodes, clip electrodes,needle electrodes and probe electrodes.
 39. The system of claim 32wherein the medical procedure is selected from the group consisting of:surgical procedures, non-surgical procedures, endoscopic procedures,fluoroscopic procedures, stent delivery procedures, aortic aneurysmrepairs, cranial aneurysm repairs, delivery of drugs, delivery ofbiological agents, cardiac surgery with cardiopulmonary bypass circuits,cardiac surgery without cardiopulmonary bypass circuits, brain surgery,cardiograms, heart valve repair, heart valve replacement, MAZEprocedures, transmyocardial revascularization, CABG procedures, beatingheart surgery, vascular surgery, neurosurgery, electrophysiologyprocedures, diagnostic ablation of arrhythmias, therapeutic ablation ofarrhythmias, endovascular procedures, treatment of injuries to theliver, treatment of the spleen, treatment of the heart, treatment of thelungs, treatment of major blood vessels, non-invasive procedures,invasive procedures, and port-access procedures.
 40. The system of claim32 wherein the means for coordinated regulation of the output of thephrenic nerve stimulator and the output of the nerve stimulator toinhibit beating of the heart is a processor.
 41. A system for performinga medical procedure, comprising: a cardiac stimulator to adjust heartrate; a phrenic nerve stimulator to control breathing; and means forcoordinated regulation of the output of the phrenic nerve stimulator andthe output of the cardiac stimulator.
 42. The system of claim 41 furthercomprising: drug delivery means for delivering at least one drug duringthe medical procedure.
 43. The system of claim 42 wherein the drugdelivery means is selected from the group consisting of: a spray, acream, an ointment, a medicament, a pill, a patch, a catheter, acannula, a needle and syringe, a pump, and an iontophoretic drugdelivery device.
 44. The system of claim 41 wherein the cardiacstimulator comprises at least one electrode.
 45. The system of claim 44wherein the electrode is selected from the group consisting of: cardiacstimulation electrodes, clip electrodes, needle electrodes, probeelectrodes, pacing electrodes, epicardial electrodes, patch electrodes,intravascular electrodes, balloon-type electrodes, basket-typeelectrodes, tape-type electrodes, umbrella-type electrodes, suction-typeelectrodes, endotracheal electrodes, endoesophageal electrodes,transcutaneous electrodes, intracutaneous electrodes, screw-typeelectrodes, barb-type electrodes, bipolar electrodes, monopolarelectrodes, metal electrodes, wire electrodes and cuff electrodes. 46.The system of claim 41 wherein the phrenic nerve stimulator comprises atleast one electrode.
 47. The system of claim 46 wherein the electrode isselected from the group consisting of: intravascular electrodes,patch-type electrodes, balloon-type electrodes, basket-type electrodes,umbrella-type electrodes, tape-type electrodes, cuff-type electrodes,suction-type electrodes, screw-type electrodes, barb-type electrodes,bipolar electrodes, monopolar electrodes, metal electrodes, wireelectrodes, endotrachael electrodes, endoesophageal electrodes,transcutaneous electrodes, intracutaneous electrodes, clip electrodes,needle electrodes and probe electrodes.
 48. The system of claim 41wherein the medical procedure is selected from the group consisting of:surgical procedures, non-surgical procedures, endoscopic procedures,fluoroscopic procedures, stent delivery procedures, aortic aneurysmrepairs, cranial aneurysm repairs, delivery of drugs, delivery ofbiological agents, cardiac surgery with cardiopulmonary bypass circuits,cardiac surgery without cardiopulmonary bypass circuits, brain surgery,cardiograms, heart valve repair, heart valve replacement, MAZEprocedures, transmyocardial revascularization, CABG procedures, beatingheart surgery, vascular surgery, neurosurgery, electrophysiologyprocedures, diagnostic ablation of arrhythmias, therapeutic ablation ofarrhythmias, endovascular procedures, treatment of injuries to theliver, treatment of the spleen, treatment of the heart, treatment of thelungs, treatment of major blood vessels, non-invasive procedures,invasive procedures, and port-access procedures.
 49. The system of claim41 wherein the means for coordinated regulation of the output of thephrenic nerve stimulator and the output of the cardiac stimulator is aprocessor.
 50. A system for performing a medical procedure, comprising:a nerve stimulator to inhibit beating of the heart; a cardiac stimulatorto stimulate beating of the heart; and means for coordinated regulationof the output of the cardiac stimulator and the output of the nervestimulator.
 51. The system of claim 50 further comprising: drug deliverymeans for delivering at least one drug during the medical procedure. 52.The system of claim 51 wherein the drug delivery means is selected fromthe group consisting of: a spray, a cream, an ointment, a medicament, apill, a patch, a catheter, a cannula, a needle and syringe, a pump, andan iontophoretic drug delivery device.
 53. The system of claim 50wherein the nerve stimulator comprises at least one electrode.
 54. Thesystem of claim 53 wherein the electrode is selected from the groupconsisting of: nerve stimulation electrodes, endotracheal electrodes,endoesophageal electrodes, intravascular electrodes, transcutaneouselectrodes, intracutaneous electrodes, balloon-type electrodes,basket-type electrodes, umbrella-type electrodes, tape-type electrodes,suction-type electrodes, screw-type electrodes, barb-type electrodes,bipolar electrodes, monopolar electrodes, metal electrodes, wireelectrodes, patch electrodes, cuff electrodes, clip electrodes, needleelectrodes and probe electrodes.
 55. The system of claim 50 wherein thecardiac stimulator comprises at least one electrode.
 56. The system ofclaim 55 wherein the electrode is selected from the group consisting of:cardiac stimulation electrodes, clip electrodes, needle electrodes,probe electrodes, pacing electrodes, epicardial electrodes, patchelectrodes, intravascular electrodes, balloon-type electrodes,basket-type electrodes, tape-type electrodes, umbrella-type electrodes,suction-type electrodes, endotracheal electrodes, endoesophagealelectrodes, transcutaneous electrodes, intracutaneous electrodes,screw-type electrodes, barb-type electrodes, bipolar electrodes,monopolar electrodes, metal electrodes, wire electrodes and cuffelectrodes.
 57. The system of claim 50 further comprising: a respiratorycontroller for controlling respiration.
 58. The system of claim 57wherein the respirator controller comprises at least one electrode. 59.The system of claim 58 wherein the respirator controller comprises aconnector which interfaces with a patient's respirator.
 60. The systemof claim 50 wherein the medical procedure is selected from the groupconsisting of: surgical procedures, non-surgical procedures, endoscopicprocedures, fluoroscopic procedures, stent delivery procedures, aorticaneurysm repairs, cranial aneurysm repairs, delivery of drugs, deliveryof biological agents, cardiac surgery with cardiopulmonary bypasscircuits, cardiac surgery without cardiopulmonary bypass circuits, brainsurgery, cardiograms, heart valve repair, heart valve replacement, MAZEprocedures, transmyocardial revascularization, CABG procedures, beatingheart surgery, vascular surgery, neurosurgery, electrophysiologyprocedures, diagnostic ablation of arrhythmias, therapeutic ablation ofarrhythmias, endovascular procedures, treatment of injuries to theliver, treatment of the spleen, treatment of the heart, treatment of thelungs, treatment of major blood vessels, non-invasive procedures,invasive procedures, and port-access procedures.
 61. The system of claim50 wherein the means for coordinated regulation of the output of thecardiac stimulator and the output of the nerve stimulator is aprocessor.